Best cities in South America to see on a layover?

I'm able to book up to 4 layovers of ~20-24 hours each in South America and I'm looking for cities that have large regional airports, decent city-to-airport transit infrastructure, and have stuff to do in the evenings and late mornings. Safety is relative but bonus points for places where tourists aren't casually mugged on a routine basis.

Anyone have any suggestions? I'd love to hear them.