If you had the job to write the next MEA, how would you ....... ?

Ehh, I'd ditch the Heleus cluster, and let Kett&Angara workout their issues on their own. Pull a Voyager, Tempest pulled into gravinanometricwhatnot phenomenon and work it from there. Inside, more character study/people under stress, failing hierarchy, lots of potential for unexpected romances.
Wouldn't honestly mind this kind of yearly release of 10 hour focused SP experience, sort of episodes/series, 30$ price range.

Jardaan are Jardaan. And they aren't source of Life in the Universe. Heleus was experimental ground for their next step of evolution and it failed.

Just big enough fish in muddy Andromeda pond. There is no hidden meaning behind exaltation, it's just their way of expansion, which turned into a self-destructing religion.

It doesn't really matter in the end, all Milky Way roots are all dust anyway, but lets go with Council for the simplicity. There is no connection with Kett, since they are six centuries apart. I know what you are referring to, but sometimes benefactor is just "a person who gives money or other help to a person or cause" and there may be more than one in the universe.

Was directly answered in-game, don't see the need to retcon this one.

You mean Ryder? Send them away on honorable recon mission, they are too much of Deus Ex Machina for any interesting confrontation.
Milky Way species are drop in ocean of billions of Andromeda natives. They need to secure their own destiny first.

Tell a story which was implied but never told. Survival. In a place where nobody wanted them to be. Dozens of thousands years old civilizations linger on mere half a million of people. And how personal dreams fit in all that.

As much as Ahriman said. The only big plothole they left in ME:A is about the quarian ark, and it will never get closure. Any new Andromeda installment must be a fresh start. For instance, they could put a N7 soldier out of stasis and send them against the Kett empire, like a new commander Shepard (without the paragon/renegade system, of course; they have to use the emotional system like Ryder). Free enslaved people, explore a whole new galaxy (not only a small cluster), try to reason with the Kett or fight them, deal with outlaws, all these kinds of things. In short, a new installment has to take the best parts from the original trilogy and ME:A.
(But who am I kidding? This idea of mine will never be a thing...)

uprightshark

If you are interested in a critique on your story, imo the premise you are using is too epic and high fantasy to jive with the 'horrors of war on the ground' take. The moment your antagonist becomes a semi-divine breed of the Titans of the Universe, your "it's just a dark & dirty survival" inevitably transforms in the "group of cool misfits saves the Galaxy"! even if their victory is miniscule, like preserving their ship and finding a safe base. The dark underhanded war necessitates the two opponents that are not really different, neither in strength, nor in morality, nor in righteousness of the cause. The moment one side is a threatening Juggernaut of Doom that is Clearly Evil, you enter the epic saga territory. Depending on what matters to you more, the Titans or the grit, you might need to look into the factions you are creating.

Armchair development is very fun

Excellent point.  It is very hard to put roughly 200 pages of draft into a few paragraphs, but I totally agree.  If our heroes go directly for the the Titan (semi-divine breed), then it is the proverbial "cat versus the mouse", the player being the mouse.  Hard sell.

The concept that I am building on is that the Titans are that pure evil backdrop to a story that could create something as evil as a reaper, but yet that is far too omniscient to bother with "us mere mortals" unless given reason, only to give context to the number of creation races (new enemy races) that will be responsible for ensuring the will of their masters and playing the role of antagonists in this series of games.  Though we would be introduced to the Jardaan and other Titans in the storyline and some key cutscenes, to add to that "we are really screwed"feeling, the PLAYER (us) will never directly engage them. 

In this fantasy Bioware project, the foe of the day is a genetically engineered warrior race called the Gorm, reinfoced by their remnant army and Jardann technology, who are engineered as the farmers and protectors of the Jardaan's newest culling stock, a new test tube race called the Veloreek in the Andromeda Cluster of Hyades.  The Titans are not native to Andromeda, so have no home planet or even settlement in this system.

The Gorm (Jardaan) and the Kett (ISHANNY), are mortal enemies and this war between them is a huge distraction that allows room for our protagonist to tiptoe amongst giants within the three other clusters of Andromeda, including Hyades, Pleides and Cepheus to try and develop the needed relationships and supports to push back the Gorm and Kett, without unleashing the full fury of their masters.  As you rightly pointed out, Titan attention will change the dynamic of the game and will become the impossible quest, when I really am trying to get at the strategy needed to achieve success without provoking certain death for all of Heleus and beyond. 

And yes, armchair development is a blast!
 

I like it that you are taking it directly from the point where the story ended and taking the risk on advancing the Ryders as protagonists further.

Eventually you maybe correct, but for the first game I would like to end with securing the new Heleus Coalition from Gorm incursion and successfully completing the humanitarian mission to save the Veloreek from being the next meal for the Jardaan, without provoking a counterattack (still to small to bother with). 

Though these are less epic objectives, they set a stage that can gradually be promoted to an epic conclusion, hopefully seeing our heroes back in the Milky Way to save the day. But there is allot of journey to travel before getting there and allot of learning and technology to get the new Heleus Coalition anywhere near capable of taking on the Jardaan.

What a blast it would be to get what is in my head on a screen .... 

Do you, guys, want to try like a weekly challenge with building our Andromeda Adventures?

Like the Intro Sequence for the Week of Wednesday 17-24th, 2018? Because I am game!!!

Oh, you know you want to! The week's just started to do the first Setting Basics like uprightshark described in the OP.

Good one, I like that!

I would not have Ryder or any of the crew return at all, save as NPC cameos.

Completely new team.

*cracks nuckles*

MEA 2: Even more Mass Effect (working title obviously)
(Note the examples I use are pretty much with my canon Ryder in mind but a lot of the obvious things could be considered choices based on what you did in MEA)
Premise: After five years of exploring, fighting Kett hold outs, and building the Heleus Cluster is more or less secure. Its been a boring yet productive five years for the Ryder twins and the rest of the Pathfinders as they are reveling in their success and with little to Pathfind they can actually relax.

Liam has moved on from his post and with the matruity he has found a new position as the head of Nexus security replacing Sloane Kelly finally in the job.

Drack has moved onto take care of the Krogan colony and continue its development and to pass on what he has learned.

Vetra has decided to stay with the Pathfinder and continue their mission of peaceful discovery, though she makes frequent stops home to be with Sid.

Cora, as always, remains by the Pathfinder's side as his second in command. Committed to protecting him and seeing them through.

Jaal believes he has found his place in the Galaxy and continues to serve in it, as he enjoys the Patfhinder's crew and company.

Peebee continues to want to see the unknown.

Gil has decided to stay with Jill and raise a family so the Tempest needs a chief engineer.

Otherwise all the crew decides to stay on to the Pathfinder.

Act 1: A massive Kett invasion is launched in Heleus, much larger then the first one, led by the Primus (now the new Archon). The Iniative Government believes that they are vulnerable and cannot hold for long so they order Ryder and the other Pathfinders to look for allies, resources, technology to fight them and the best place to look for those is beyond Heleus. But first they need the tech.

They manage to follow a lead and hunt down the Benefactor. The Benefactor has technology, advanced, that will let the Tempest travel much more quickly to other clusters. But she does not want to give it up for her own reasons. A firefight breaks out and she manges to escape, but Ryder and co manages to secure the FTL drive and incorporate it into the Tempest's systems. However she is the only ship that can successfully integrate it for reasons.

So they head out into the Greater Andromeda Galaxy looking for allies.

Act 2: Ryder and co stumble across a planet in the middle of a new cluster with a sentient race on it. This race has suffered greatly at the hands of the Kett. They do not want to get involved however but point the Tempest and their crew in the direction of a planet that they believe can help them.

When the Tempest jumps into the system though they find out its the Kett home system. The Tempest is quickly surrounded and captured by the Kett and brought to the planet surface. There they confront the Archon who tells them of their plan to exalt the crew. However because of SAM it makes it impossible to exalt Ryder, so he will just have to wach as they exalt one member of their crew after another. They start with Suvi and Cora, as they are both humans.

Eventually Cora and Ryder reconnect though and she talks about her experiences with the Kett, how she believes she is starting to break, and bits of her skin even look bony and calcified. But while Ryder is being moved to a new facility they are attacked by a group of other Kett who manages to break him out.

They explain that the Kett exaltation was a tragic accident. A group of scientists long ago was trying to perfect and advance the race using bilogical technology they had found, but it got out and infected the entire species, it sterilized them. This divided Kett society as some saw it as their duty to bring this 'gift' to the rest of the Galaxy while others merely viewed exalation as a neccessary evil trying to find the right combination of genes that could save their people and restore their ability to reproduce.

Ryder acknowledes that and the rebels say they can get him off the Kett homeworld. He refuses saying that he is not leaving without his crew or the Tempest. They say this is suicide and Ryder has an idea, to send a distress beacon to the Iniative asking for help.

It comes in the from of Drack and a bunch of Krogan who manages to break the crew out of their just as Cora is about to be exalted. They manage to get them to the Tempest and off planet but now Drack is captured.

The Kett leader of the resistance has to flee with them and she becomes a new member of the crew,albeit quite resentful.

Little later on they discover Drack has become exalted himself and is now one of the principle agents of the Kett.

The Kettwoman points them to the direction, one last piece of desperate intelligence to where they believe might be the Jaardan homeworld. A place forbidden for all Kett to go.

Ryder, fearing another trap, sets a course because it is desperate, the situation in Heleus is growing truly unstable as the Kett almost captured both the Nexus and Aya leaving several people dead.

Act 3:

Ryder goes to the Jaardan homeworld and finds the scourge everywhere, but also a dead and decrepit city. Suvi swears she discovers life signs below the planet surface so they land. Ryder manages to wake up the Jaardan and pleads for their help. Instead the Jaardan thanks them for pointing the way to Heleus, that they will begin their purge of all uknown threats. They leave them alone though considering the Tempest is slow and unknown. Their ships rise from the ground and head off towards Heleus, a war fleet that will destroy both the Kett and the Iniative.

The Tempest leaves after them, racing to stop them. They arrive just in time to see the Jardaan absolutley going through a fleet of Iniative and kett warships.

They have to board one of the Kett flagships where they fight both Drack and the Archon, killing both and liberating part of the fleet, beginning to coordinate their actions against the Jaardan. But, the Jaardan prove to be too much for them.

In short order the Tempest is destroyed, Kallo is killed at the helm, the Nexus and Aya are captured and things look very bad as literally everything comes crashing down around Ryder's ears.

Which is where the game ends...to be continued in MEA 3.