^You can pretty much tell that just from the game mechanics; it being the "hardest" pathway to unlock. Regardless, I don't see how the magical rainbows and unicorns world we saw with than ending could be a viable setting for another game. Dramatic stories require conflict, and it's really hard to have conflict in some post-singularity utopia. Even if they set the new game tens of thousands of years later, the consequences of those endings should still be apparent. That leaves three basic options: 1) Pick "destroy" instead 2) Dramatically retcon what synthesis entails and 3) Do a prequel.
While a prequel would probably present the least amount of problems (especially if they're steering clear of the space marine angle) I'd rather see some consequences of the previous games.