I'd make the following changes:
-No more HM's. Replace HM's like Cut, Rock Smash, and Flash with items like an axe, a pickaxe, and a lighter. Things like Surf and Strength should be done by big, strong Pokemon, and Fly can be done by flying Pokemon that look like they can carry humans.
-Make all Pokemon available in one game. Replace trade evolutions with different evolution methods. Trading would still be an option if people want certain Pokemon earlier.
-More postgame. Plenty of sidequests, a Battle Frontier, a PWT, some new areas to explore, etc.
-Difficulty options. Easy for beginners, Normal for casual gameplay, and Hard for people who want a challenge.
-Allow the player to deviate from the "get all badges, become the champion" thing, and become a Pokemon Breeder, Coordinator, or evil team member instead.
-Make it easier to see which EV's your Pokemon have.
-Make the DexNav show a wild Pokemon's nature beforehand.
-Balance the type chart. Give the Ice type more resistances, make Dragon type moves hit more types super effectively, make Psychic resist Fairy, make Fairy no longer resist Bug, things like that.
-Balance all fully evolved Pokemon to make them viable in competitive gameplay. Only big legendaris like Mewtwo, Lugia, Dialga, Kyurem, etc. should be OP compared to everything else, and make up the Uber tier.