1) Pokemon need to be able to use more than 4 moves. See VG Cats for the point (nail on the head). 6 would be an improvement, despite being still low. Honestly, Pokemon needs to take a page out of Legend of Mana's book. Once the move is learned, it stays permanently in the database for that Pokemon so you can reassign which moves are active at any time. 8 moves would be nice, and some of those situational and status altering/support moves would finally get played.
2) Serious rebalance. Is your Pokemon at it's final stage of evolution? Is it's level at least 10 levels higher than your opponent's pokemon? Have you doped it up beyond the max? Is it bred through the day care center and raised loving you like a god? Is it an uber pokemon? Is it shiny? Has it had pokerus? If not, your pokemon aint's shat; GTFO! There may be 400 pokemon, but the number of those pokemon that are actually useable is in or under the 5% mark once you start playing real humans. This game needs serious stat balancing and pokemon need incentives to stay unevolved or to evolve. Example: Why is the hulking giant form of each pokemon so much faster than the small version? My cutesy squirtle should be dodging attacks and taking 3 moves for each of my Blastoise's moves. And tank pokemon should have a 0% evasion rate. How is the 10 ton Onix evading my Thunder/Ice Beam, Blizzard, Fire Blast, etc? No, no, NO! Balance.
3) HMs must go. I can only carry 6 of the 400 pokemon with me. That's a maximum of 12 of the 20 something types (ick, dual types). I cannot afford to keep a minimal 2 HM whores with me at all times just because I might run into a tree or puddle on the way. I don't care if they want to keep putting up trees and water as road blocks, but if I have a flying Pokemon and the badge, then let me fly. If I have a water pokemon or a pokemon that can swim and the badge, then let me cross the water. Ditto, if I got a pokemon with razor sharp claws and it knows Razor Leaf, Slash, X-Cutter, and Swords Dance, then dammit, let me cut down that tree without the crapsack cut HM. HMs hurt the game several times over.
4) I want to do more with my pokemon than fight and have lame beauty contests. Overload the game in minigames for my pokemon to grant me access to. I want a water gun target shooting minigame, like those things at the carnival where everyone races to fill the balloon/meter first. And how about a grass pokemon weed wacking game, where we clear out grass/trees/vines/bramble/etc. And a strong pokemon contest where pokemon compete throwing boulders, pushing heavy objects, lifting weights, etc. And how about a flying minigame where we fly through rings or something. Let my pokemon do more than fight. Level gridning sucks, and I can't use 99% of my poke favorites thanks to the balance issues, so give me soemthing to do with them and a way to break up monotiny.
5) I want to be able to have rematches with gym leaders and all other trainers, and I want them to continuously grow and cycle through their entire collection of pokemon to keep me guessing. If I know my entire opponent's line-up and move list, I WILL exploit it. It's like forcasting rock 100% of the time. I WILL use only paper. And how about we get this leveling junk under control: I want every opponent I face to have pokemon as close in level to mine as possible (give or take a level or two). No more running into overwhelming or underhwhelming opponent's. Wild pokemon should also have the good sense to not pick fights they can't win. Level 2 Rattata and Level 3 Pidgey need to know not to fudge with my level 80 Tyranitar and friends. Seriously, it's like baby bunnies and ducklings starting crap with a pack of tigers. It ain't happening.
6) Balance the move set. There is no reason for me or anyone to use any of a list of 20 moves than do under 95 damage, when we have a 95%+ accuracy move of the same type with equal or more PP in that same type. Why use Stomp, when I can do more damage with the more accurate Headbutt, and it causes flinching? Why use Water Gun or any other water move when I can just spam Surf? Why use Sand Attack when Mudslap causes damage and lowers accuracy? The moves need balancing. And there's no reason the starter move set, if not all moves, can't level up as well. Level 1 water gun is fine for starter Mudkip, but let it level up until it is as powerful as Surf, and I might keep it around and use it.
7) No more bikes. No more fishing gear. No more multi-function gimmick box poke-whatevers. Just gimmie my pokedex. Make me choose a scan option when I meet a new pokemon to record its data, and let that be the end of the gimmick gear. From there, I can ride my pokemon, walk, or run. I don't need all these crappy useless functions and items clogging my bag. Enough already.
8) Speaking of enough, how about a new story for the first time since Red/Blue(Green)? Every game has had a rehash of the same story. No more. New story now.
9) End random battles. I want to see the pokemon on the field, and I want the option of avoiding them, being ambushed, or ambushing them. This is especially true of caves. I will never play another Pokemon game as long as caves are teaming in random Geodude and Zubat encounters every 2 to 5 steps. NEVER AGAIN!!!
10) 100% of the entire roster of every pokemon ever made needs to be available in a single game; not this 100/400 possible pokemon to catch crap. Also, no more dual games crap. Make a single pokemon game with all the pokemon, and let players trade if they want to. Stop forcing the gimmick that no one uses (because cheat devices are faster and easier). I don't want to choose between Pokemon Amethyst and Aquamarine. Just give me Pokemon Rainbow, and let me enjoy my fraking game. If you must make attaining 100% of the pokemon's harder, add a randomizer that scews the odds for finding rare pokemon at the start of each new game, so each player's game has a different list of hard to get pokemon. Or, instead of beign jerkasses, just make the game a huge open world with the player starting dead center, and spread the 400 pokemon across the entire world in their own territories. Players heading south will trade for those northern pokemons, while eastern adventurers will trade for those western pokemons, etc.