I don't think a sequel *couldn't* work, but it would seem to go against everything they said before and after ME3's release - that this was the opportunity to make decisions that would have lasting ramifications for the galaxy. The cinematic designer for the Extended Cut mentioned that some of the ending slides were set decades and centuries after ME3, and the November 2011 version of the ME3 'script' seemed to indicate the Buzz Aldrin/Grandpa scene was up to 10,000 years after the game ended - as if they were showing the far future of the universe because they never planned to revisit it. Shepard changed everything, forever, and whatever comes next is up to the player to imagine.
That's not to say Bioware couldn't have changed their minds in the meantime, but from my perspective a sequel that somehow manages to not mention anything about the endings or their consequences seems like an awfully hard contortion. It also, for better or worse, would dilute the impact of Shepard's entire trilogy, and diminish the impact of that last choice - if everything turns out pretty much the same, what was the point of making it?
If in 200 years a synthesis-utopia, GodShep flying around, or a status quo-minus-the-geth universe all turn out to be the same thing, or similar enough that they can be differentiated by different NPCs scattered around, that seems... a pretty humongous anticlimax for the end of Shepard's trilogy. The Catalyst and the EC narrators spoke of Shep's choice changing the galaxy forever - I really don't think those sort of wild diverging changes can be reconciled in one narrative, not without retroactively undermining their importance and impact.
Wowky wrote..
And actually, if it's not going to relate to the Shepard 'universe' in any way, then it can't really be a prequel either.
How do you figure? A prequel doesn't have to involve Shepard or any of the characters we know, by definition it just needs to take place before ME1 in the timeline.