I think whatever we do has to be more complex than just 'factions fightin.' That strays too closely to the old iterations of the multiverse. 

The big question, in my mind, is what setting do you choose? Do you try to create something that allows every type of character in, and deal with the absolute shit storm that will eventually unfold due to inherent mismatches? Personally, I've always been inclined to create something a little more contained. A medieval fantasy world where the characters all start at a reasonable level, human peak with spells or abilities limited in scope but with the potential for growth. Its a world where the most variety of characters can exist, at the cost of anything more technologically advanced than black powder weaponry.

Then, if desired, you start weaving in other settings for different character types to engage in the story. There is no reason whatever overarching theme can't be carried over to a world more advanced in technology. But to start with, keep it simple. 

Just my feels on things.