Personally, I would love freedom to be in the next generation of pokemon. Have the choice of being the good guy, or being on the bad side. Having different choices during your adventure would be amazing. I seriously would love to be on the evil team for once. Also, having new starter types, instead of Grass, Water and Fire all the time, would be nice. Having the choice out of Grass, Water and Fire every generation is boring now :/ I would love different types for the starter.
I think water, fire, grass, and electric starter choices would be a nice twist.
I enjoyed seeing Bulbasaur, Charmander, Squirtle, and Pikachu in their basic stage in the Kanto Anime. Red, Blue, Green, and Yellow feels more complete, albeit, not a rock-paper-scissors matchup.
Though, I don't know how my nostalgic side would recieve a game that didn't offer at least the grass, fire, water choices!
Another alternative would be a Water/Grass, Grass/Fire, Fire/Water trio. This could certainly have mixed receptions by longtime fans, but it could be pulled off.
Aside from starters, I would love to see a Coastal Mediterranean Region. Start in Spain, move down to Italy, then go along the perimeter through Greece, Israel (Palestine), Egypt, Add the Congo somewhere near Algeria/Libya (I'm sorry I need a jungle!), Morocco, Portugal, then surf out to Cyprus for the E4. I love the ancient history in this part of the world (branching from the Fertile Crescent/Mesopotamia, and converging continents. It would be refreshing to take a step back from the modernized regions based on Modern-day US and France.
Also, XY, though I LOVE it, was too...French. I would have preferred a mixture of cultural influences, like England, Spain, Belgium, Germany, Ireland, Switzerland, ect.