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Time to start a shameless plug for my home region. I think British Columbia could make a good region. Vancouver would be the central hub of the region, the city has a unique look to it with the way it interacts with nature with several interesting looking buildings, (BC Place Stadium, The Vancouver Convention Centre, Science World). The Battle Frontier could be Vancouver Island, the Elite Four could be in the Rocky mountains, the Capilano Suspension bridge could make for an interesting area, they could turn Grouse Mountain into a sort of Black City/White City from Black and White 2, as it would be fitting as there is a thing in the real world called the Grouse Grind. There is plenty of native lore that could make for good legendary pokemon, the story could be something about learning to live in balance with nature or something equally corny as that. I think it would be an interesting environment for a pokemon game, plus homerism.