What should the next Mass Effect game be about?

I'd almost like to see them try something new akin to Halo Wars that's about the First Contact War.

Otherwise, I think we're in Andromeda until some Andromeda threatening threat comes in and ME7 reboots us in a fresh galaxy where the Andromeda people said "We need to colonize new worlds, 800 years in the future and a billion light years away"

Ehm... can we wait until ME:A is out first for everyone?

Its the Dragon Age approach, which is what they should've done with Mass Effect to begin with. Now they have the chance, and they should stick to it.

Unless it's a spinoff in another genre, which BioWare would never do because there's no reason for EA to waste the RPG pedigree on some other genre, we'll be getting a sequel to Andromeda. If BioWare are ever going back to the Milky Way, it won't be soon, prequel or otherwise. Quite honestly, that's how it should be. Why go through all the trouble of setting up an entire new sector of space if you're just going to toss it away after a single game? We left the Milky Way for a very good reason. If the franchise should continue at all, it should continue where it has the foundation to.

I also wouldn't expect a mainline Mass Effect to be from an alien perspective any time soon. BioWare have been pretty explicit about the how important the human perspective is to the franchise. The most I'd expect is race options in the CC, but even that's a stretch. If Andromeda is in any way a success, I don't expect we'll drop the Ryders any time soon.

They also said this was the beginning of Ryder's journey. They've been strongly hinting at the fact that they are planning on Ryder being the protagonist in more than one game. 
Again I doubt they'll switch from Ryder to a new protagonist to begin with. This is Mass Effect, not Dragon Age.
And you saying it's what they should've done is opinion. I prefer Mass Effect over Dragon age just for the fact I can look forward to playing the same protagonist again.

sequel to ME3.

My personal favorite is to remake the trilogy.

Prefer MEA sequel. Also interested in an origins (take us back) style game.

I think it eventually happens.  Depending on how well MEA does, it could be sooner rather than later.

Return to Milky Way with a new perspective and new intrigue on WTF is going on there.

This doesn't mean no Andromeda. Maybe have that too.

Have an outgoing look that considers galaxies beyond both.

Bioware's "Been there, done that!" approach to Milky Way is super stupid and I even hope the PeeBee that says it has some other meaning behind it other than her choosing to be stupid. At the same time, sure, don't *restrict* yourself to just that location.

I've never been against going to another galaxy, but I just want it to make sense, I want the series not to forget it is a series, and I don't want the older region left behind.

I did get a little hope when I heard that eventual goal of Initiative is to find a way back.

Expanding a fictional universe a lot is something easily welcomed by me. Running away from it and not looking back... not so much.

I'm okay with an Andromedan focused arc. But I prefer it incorporates a lot from the trilogy and if it somehow gets super weird (I don't know, but just bizarre concepts), I'm even open to meeting characters from the trilogy in some form. I. Love. Continuity. Too bad Bioware is spotty with it for some major things (jesus Revan...you suck). But I like it.

I already want to see more of Ryder's story. I don't want my choices to mean nothing.

If Andromeda is a success, more probable is Andromeda sequel. It is imo a bit early for such question.