I'm sure I am not the first person to think about this but, wouldn't it be simpler to cannonize one of the 3 endings ?
From a continuity standpoint, if we want to keep having rich stories with challenges(that we, the players can relate to) to our characters, I say the only viable ending we could have is the destruction ending.
If we choose either control or synthesis, the milky way will still have a giant armada of friendly reapers to protect it no matter the threat the writers think of. If they find a loophole to remove the reaper protection, it would undo what these endings have accomplished anyway.
And with the synthesis ending, we are stuck with one hybrid bio/synthetic race. From a scifi standpoint, usually you create alien races to put some diversity, visually and mentally, in your story so it gains dept. With synthesis, you loose all of that. You don't even have the human race to act as "anchor you can see yourself in"...
At least with destruction, we have mosts races battered, but alive. You still have an entire galaxy to rebuild and still explore, and most of all, you can still give a challenge to the characters that isn't too gigantic in proportion because you don't have to take the reapers into account. And with at least a canon ending, it is much easier to link andromeda to the milky way in future games, because, honestly, I don't see the point of exploring another galaxy if I cannot tell the tale to the people that sent me in the first place.
It's like stargate atlantis that never called back earth, it wouldn't make sense...