More likely that we're heading back to the Milky Way?

Eh I want them to. It be a gigantic waste if they don't.

Is there really a difference? A good or bad game won't really be determined by whether or not they continue with [at least most of] the characters or setting anyway. 

I sincerely hope they do not pander to the screaming minority and return to the Milky Way. That would impose a canon ending which would negate much of the storytelling upside of the original trilogy. That would be akin to a direct sequel to Baldur's Gate 2 imposing a canon ending and making user choice irrelevant. As clunky as the writing was for ME:A they have a decent premise and an intriguing new setting with more possibilities. Roll with it.

This. I honestly cannot get my head around why anyone would think that returning the series to the Milky Way will make anything better. We've literally got a galaxy three times the size of MW right there in the game and MEA has sorted the intro part. The MW is done, now. The OT answered all of the big questions over its run.

I mean ideally, head back to the Milky Way, canonize Destroy as the canonical continuity of the ME verse, take it from there.

I mean sure not directly, but I'm inspired by their handling of the setting and characters in the first one, why would I think they would do better going forwards?  Unless they Red Wedding the entire cast and shove off to a new cluster

If you canonize an ending for the ME trilogy you pretty much explosively deficate all over those games. Plus, the "well it's big enough" isn't really valid for continuing in the Milky Way. Travel was far too easy by that point to protect the trilogy ending and leave it there. 

I don't understand how some can't see that some group of people with means would want an "exit strategy" for humanity in case of failure. Seems pretty obvious to me. For those who lament the the bad (even by video game standards) writing in much of ME:A they can't see how staying or returning to the Milky Way is infinitely worse as a premise before there is even a story to screw up.

How on earth would this fix anything?

I just don't see a canon ending being the answer. You go with Destroy, which I agree would be the easier solution, you're going to destroy the stories of anyone who picked Control, Synthesize and, though it was added later, Refuse. I can't see doing that as getting fans to buy into the game premise any longer. If anything it'd chase fans away and that's just throwing away money.

Well tough shit for them.

I know this isn't going to happen, I'm just saying what I'd like, not what is feasible

true, but I want more Mass Effect, I just don't want more ME: Andromeda