Like I said, I don't think following up the Reaper War with yet another massive conflagration is a good idea. Down the road a ways, maybe, but not from the outset.
I'd prefer them to tell a smaller scale, more personal story. Think 'Firefly' in terms of setup and stakes. No big galactic fleets (unless you're either stealing from and/or running away from them) no unfathomable cosmic threat from the unknown reaches of darkspace and I think most importantly; no uniforms. I'd like the next ship and crew I play in the ME universe to be a civilian one. Sort of like what was done with Dragon Age 2 (not the best example, I know.)
It'd also be nice if you get to pick your character's race, but that might be too resource intensive to pull off.