^Not much danger of that. As I said, there's really only a 30 year span of history between first contact and the Eden Prime attack. We pretty much know about most of the big stuff like Shanxi, the Skillian Blitz etc. and none of it is really viable as a setting for an RPG. A sidequel set in the two years Shepard spent dead might be a possibility, but again, we know that nothing much really happened so the scope of any story would be very limited.
To me the most likely scenario is to set the next story centuries or millennia after the events of ME3. The latter if they want a complete break and the former if they want characters like say Liara as a matriarch or Grunt as an aged battlemaster to make an appearance. Either way they'd need to pick a canon ending and that's unfortunate.
I suppose they could try and dance around it like (from what I gather) happens in the Elder Scrolls games, but honestly I control, destroy, synthesis and refuse would be next to impossible to reconcile.