If you would consider having to start over with a new team per region, why not just have separate games the way GameFreak did? That way, each one could be built with a new/improved game engine. As far as the back end goes, I think it would be a safe guess to say that Nilllzz has at least a few things he would do differently now if he were able to start over (not suggesting he should). That way, with each game, we could enjoy engine improvements as well as be able to explore new regions.
My brother makes games, and he is stalled on his 'big' project because of all he has learned between when he started it and now. His programming paradigm has changed so much, it makes it difficult to keep working on it the old way. I think something similar might happen here if all the regions were put into the same game.