Give the save system in ME1- 3 it is obvious that no saves will be tranferred. No saved = no ending tranferred. So they either pick an ending; destroy being the only plausible starting point for a game taking place in the short term.
Bioware will announce that high EMS Destroy is the cannon ending. They announce that the others are indoctrinated endings a day after the final DLC is released for ME3 and therefore they will not be used to continue the franchise. Or simply make Destroy the ending they will contiue from and don't bother to address indoctrination. But I think if they have any respect for their work and self respect as writers they will admit that synthesis, control and refuse are indoctrinated endings. And maybe even add new versions of destroy as free DLC: destroy, destroy-control and destroy-synthesis. There is absolutely no reason control or synthesis need the reapers to remain. Control and Synthesis being options in lieu with destroy makes them true sacrifices vs. just what people do because they think Destroy will kill the Geth.
Or the game needs to be far into the future. Probably in Stargazer time.
Bioware has stated that synthesis will occur at some point regardless of which ending is chosen. Furthermore, the Stargazer states that the details concerning the exploits of The Shepard have been lost over time. This, in essense, questions even if the ending you picked is what actually occured becasue the exact details have been lost over time. The ending the player chooses is just the Stagazer's telling of the story. It doesn't take a rocket scientist to see where this is going.
The next game in the franchise will take place in the distant future.
In this distant future synthesis will be a reality achieved on our own terms, albeit no glowing eyes and circuit skin. I believe the glow was included to make the outcome visually distinct from the other two. When or how we achieved it will be vague however. This allows for ending ambiguity. This way the player can think maybe it was from synthesis ending; maybe it occured after Destroy or Control.
In this distant future the Reapers will be things of legend. They either were dismantled, left for a new galaxy, were destroyed or whatever. Like the archangel Samael they will be villains in some legends and redeemed heroes in others. No one telling of the story will be given legitimacy over another. This allows for ending ambiguity.
The Geth will still be around. There is no concrete evidence that the Geth are wiped out in Destory. Regardless of rather you side with geth or quarians, there were survivors and those survivor went on to repopulate the race. Peace was achieved at some unspecified time. The Krogan genophage will be cured or overcome naturally at some point in the past. They may even have the Rachni sharing Tuchanka with the Krogan. Or they may just make certain outcomes canon without explaination.
The Shepard's sex will be unknown.
They could also have an event in game similar to Miranda's questioning of Shepard on the shuttle to the Cerberus base in the beginning of ME2. Where a history discusson is taking place and the player states what they have been taught. This would make minor changes to the codex and a few dialogue changes that make no real difference. I could see the game opening on one of the cut off worlds. A fleet has recently arrived after centuries to repair the relay and introduce the lost colony (which is now a city world like terra nova) into galactic community. This way the player gets to be wet behind the ears.