How is Bioware going to keep everyone happy ? ....well i don't know if they are, but there has to be a foundation on which to negate a backlash, and that would be to dismiss any idea that the next game could be from the back catalogue of stories. I mean, yes there are loads of historical stories on which to chose from, but there is also plenty of room to create future stories connected to historical events, or preferably do a new story in the same universe. There is no getting away from the probability that no matter which historical story you play, people will be thinking "oh you think this war is bad, just wait until the reapers show up", or "i know what happens, i've played the trilogy before and i've read the codex, you guys win".
The people who think you'd be as well making a new title instead of having a new story or no Shepard are missing the point, if you lose Mass effect you lose all the different races we've became accustomed to. We were one commander, with a team. However, they were not more important that the billions they set out to save. The people who think that Shepard is Mass Effect have a similar thought process to the Illusive Man. Oh no the humans died, let's not go on anymore as he was obviously alot more important than the billions of others he saved.
As Bioware take ideas and concepts from factual and fictional events, then the answer is simple. You can create a Mass Effect 4, but the threat doesn't have to be as huge as the reapers. It's not as if the world was at peace after Germany was deafeated in 2nd world war. There have not been wars of the same scale, or of the same magnitude, but there have been significant wars. I'm sure something involving a conflict between Leviathan and Javik could make for interesting gaming, as just one example.