I'm honestly really curious about this. Where the hell is game freak going to take pokemon for a fifth generation? We've gotten to the point where we have pokemon that are literally creationist gods, capable of altering reality itself -- and you can catch them in a little ball and have them fight for you! It's hilarious! Where can you go after this? What could be grander than the Dragon trio, Arceus and the creation myths of Sinnoh?
The only thing I can think of that seems halfway interesting is to do what Klaatu said and try balancing out the existing game by trying out some new type combos, giving more physical/special moves to types that need them, expanding the possible abilities a pokemon can have, and generally trying to level the playing field so that there are less "bad" pokemon and types. Story wise, they could try balancing out the heavy mythological stuff from Sinnoh and the god complex/sociopathic power trip of Cyrus and Team Galactic with something a little lighter and more laid back, maybe some good old fashioned Rocket-style thievery? Or hell, if you want to keep it fresh, let's delve into the forces at work behind the creation of artificial pokemon like Mewtwo. I'd love it if the next "team" to appear were a group of mad scientists and you had to battle their new, synthetic pokemon before being able to capture them for yourself. Man, game freak should totally give me a job. :bidoof:
As for gameplay, if we're talking about a next-gen handheld after the DS, the obvious thing to do is to give us fully animated 3D battles already for chrissakes. They could have conceivably done this with DPP and instead chose only a modest graphical upgrade over the advance games. There isn't much ground left to break in the world of Pokemon, and this is one of the few things left that they could do to make Generation V into something more exciting than "just another hundred or so pokemon in a new region"
As much as I love these games, the same old shtick is getting old and they're going to have to introduce something revolutionary with the next generation if they want to give the franchise a future beyond that.