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All Gym leaders have a full team with proper skillsets and atleast above average IV/EVs
Random shitters have any number between 1 and 6 with lower numbers having higher levels and better stats/moves
Limited item capacity, your backpack is no longer a bottomless pit. Each pocket can only hold X amount of stuff. You can switch packs out as the game progresses that alter the distribution
All TMs are one time use (can be found/bought/aquired again). HMs are permanent but you must be at a PC to use. Breeding and move tutor remain unchanged.
No HM slaves but you must capture and train a poke to use the HM and it becomes a summonable thing as in SM. none of that bullshit safety gear, just unblemished and raw human on poke action.
No story handholding past the first startermon handout. Your goal is to beat the E4, end of story. if you make a rival along the way its beacuse you sought them out not that the game decided it was time for a dialogue wall with mandatory roleplay battles. you can go back to ez mode if you want spoonfed story.
No arbitrary roadblocks, if you walk into the lv 60 dragon cave and your lv 10 waifu gets creamed, tough shit.
All status effects last after battle, poison, burn, all of them will wear off after some time, even standing still. To balance this, healing moves (Roost, rest, synthesize, ect) can be used in the overworld and fresh water springs and other wild survival type means added to the map that heal/cure conditions. Berries also work and scale to some degree based on the mon its used on. Berries greatly increase in availability in wilderness zones.
You can only fly to areas with an airport and not all pokecenters have one.