Regional culture, where possible.
Say you have your starter town, and town in the distant north, and a town in a deep jungle.
Obviously these places look different environmentally, but many people will use the same NPC's for each place. When resources allow they might have them wearing parkas and such in colder regions or something like that.
But I think it would be a pleasant effect to go a step further. For instance: maybe the world population does not consist of only WHITE PEOPLE. And I don't mean just slapping slanty eyes on the denizens of asia land. Get creative. Make up some features of your own. For instance, in the illusion of Gaia there were a small, almost extinct race of people that could not come above ground, lest the sunlight destroy them. (A trait borrowed from vampires or, arguably, albinism, but interesting nonetheless). That was pretty neat.
Now extend it a bit further. Say you have your chinatown set up. Then...that's the only place you see chinese npc's? What? All of the world's chinese come from a single village? This is another little 'wrongness' I see crop up even in professional product. Why not make all of the towns on a given -continent- share a theme? Doesn't that make more sense?