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-Start from Gen 1 again.
-Humans live in closed off city states for protection.
-Pokemon are demi gods that humans can't compete against. You need friendly pokemon to venture outside.
-Trainer battles aren't the norm. The only people you battle are criminals that enslave pokemon, and police that use pokemon.
-Trainers standing in the wild that approach you are replaced with pokemon that are exceptionally strong or have unique TM like abilities.
-You gain money from selling captured pokemon. Prices differ by area.
-Day night cycle, four seasons cycle, certain pokemon appear depending on cycle.
-You can only save at camping check points in the wild or hotel rooms in cities. Points are plentiful - but certain areas aren't so be prepared to push through.
-Your pokemon die, not feint, against Team Rocket. Dead pokemon have a chance to be replaced with a Ghastly.