One of the strengths of Pathfinder is the feeling of cohesion that the products have, and this is largely due to Golarion. Similarly with Midgard and Kobold Press, although it is less comparable to D&D in that has far fewer products.
I like what
@Minigiant said, but would alter it slightly. Have a core setting that is built from scratch, and then offer alternate settings ala the current publishing schedule. But I think the game would have a more cohesive quality if the rules were embedded within a context, rather than in abstract "D&D Land."
A new core setting would also allow for WotC to adjust the lore in a way that wouldn't freak out "setting diehards" ("That's now how elves are in the Realms!").
But that only works if they offer alternatives, otherwise it becomes a kind of codified One True Wayism. We don't want D&D to be forced into a singular modality of play (well, most of us don't). And furthermore, it should be emphasized in the intro of every rulebook that this is just the default mode - make the game as you want it to be.