I think many of us are looking wrong at the endings of ME3 in the sense, that when making the choice we rationalize why it is the best solution in our opinion.
For example I take destroy, because I'm not sure if I (my Shep) can control the Reapers forever (so there is a possibility of them becoming the deadly threat they are again) and I would never force a DNA change on the galactic community. So of course I think of future scenarios that are totally different in all three scenarios.
Going forward in the ME universe that might not be though what Bioware is doing. They might say: all three endings are valid solutions to the Reaper threat. That means what they have in common is that the Reaper problem is solved.
1) In Destroy there are no Reapers anymore.
2) In Control the Reapers have vanished.
3) In Synthesis the Reapers have fulfilled their purpose and will for example be deactivated (maybe they even self-deactivate after their mission was successful, i don't know).
Ok, so Reapers are no more. For the survivors destroy and control are the same, the only difference initially might be that there are no Geth (though as machines they could be rebuilt) or that the Quarians are low in the numbers (even if you side with the Geth, not all Quarians are with the Flotilla and not all Quarians would die if they lose the war with the Geth anyways).
So what does that mean for the next Mass Effect game? That Geth and Quarians won't play a central part. Nothing more. Doesn't even mean that you can't have squadmates from these races, just that they are not central to the plot as a whole race.
Genophage cured or not? Even simpler. Just because your Shepard decides not to cure the Genophage, doesn't mean that the Krogan don't succeed with their main goal later. Yes, I know, Mordin thinks that "someone else might have gotten it wrong", but that doesn't mean that the writers can't come up with another crazy good scientist finding a solution later on.
Ok, so the major differences are no problem going forward if we think of destroy and control at first. Remains synthesis as a possibility. Though I think of it as raping the galactic community to say it clear, that again (and the epilogue for that ending suggest otherwise) might not be how Mass Effects writers see it. To come up with a solution for this they could for example say: if you choose synthesis as starting point going forward, the races get powers they hadn't before, because now they are "half man, half amazing" - I mean "half man, half machine". So when customizing your new hero you could probably choose from a wider set of powers than when you choose destroy or control. I still wouldn't choose it, but hey, that would even underscore their intention of synthesis being the best and inevitable solution.
Being green you say? Could be a side effect that wears off or not, shouldn't be too hard to implement in the game. A non-factor when you wear your armor and just green eyes for everyone in cut scenes if it doesn't wear off.
Alright, Reapers are gone, every choice at the end of ME3 is valid going forward and has nothing to do with the new conflict.
So here we go: setting? To me from the concept art and other info (new races will be discovered) it looks like it is after ME3s ending, but not too far ahead because of the return of the Mako. We heard that it will be a hero's journey, so we will start at an earlier point in a career path than we did with Shepard. The conflict might arise with at least one of the two new races, obviously it is likely with the one with that dark, mysterious hub.
An early guess: "After the Reaper threat was solved, the galactic community explores not seen before regions in the Galaxy to get new resources for the rebuilding effort. And they thought they where safe..."
I love how much time and energy people put into their decisions.
Mines simple, job was to end the reaper threat. didn't even consider the options, "sure you could destroy us" "thanks kid" *fires*





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