I really love the ME Trilogy characters, but I have to agree with @ThandalNLyman with this, I MUCH prefer they continue into Andromeda and all the interesting story lines they have there. We have done the Milky Way, and to me trying to top the big bad of the Reapers would be not so good of an idea, a smaller scale ME doesn't really seem to fit the series, and if you just make every ending of ME3 turn into the same setup it lessens the impact of ME3 endings. Who cares if you destroyed the Reapers, now control them, or if everyone is part machine....you are all in this XXXX staring space in the new Milky Way ME5!!!!....yeah, no.
Also as Thandal said, 600 years is like 40 or so years in human scale for them....while things would have changed a bit, it wouldn't be enough to overhaul individual ME3 endings. I think if they put the effort into a really good game, a sequel to MEA could do well, as long as they don't make tired faces and don't try to cram too much stuff into the game, let it build over multiple games.