see http://www.quora.com/Hows-life-in-Santiago-Chile for more background.
i am here because my partner is a chilean academic with tenure here. in general, it's a good place to live. personally, i am not the most outgoing or relaxed person on the planet, and sometimes living in a different culture - and it could be any other culture - gets to me. but the only negative thing i can think of about living here is that the work culture in large companies (my first job) emphasizes hours over productivity. if i were coming here to run a startup i would use a more results-oriented working environment (i don't care if you work at home, but you fucking get stuff done) as an incentive. a lot of people really hate the enforced long hours.
you need to speak spanish. but people will be friendly and tolerant when you screw up. you can learn while you are here. a chilean lover is as good a way to learn as any ;)
PS - just thought of a negative (as i went outside). the winter air quality in santiago is terrible. if you have asthma you don't want to be coming here. another negative would be the differences in wealth, although i imagine that's more shocking to a european than an american (i have no idea why i am paying such low taxes compared to europe - why isn't more of what i earn being used to help the poorest people here?).
PPS - some positives: good food (you have no idea how good a hot-dog can be); good beer (really - it's exploded the last few years with a bunch of micro-breweries); a more entrepreneurial attitude than europe; a more sane social attitude than the usa; low crime rate (despite what people here seem to think...)