I never played Civilization III, so the jump to IV is enormous. Somehow, the game has gotten more insanely intricate and deep, but it's easier to play than previously and presents land management in such an approachable way that city conditions and labor aren't ignorable anymore. Plus, the religion system is maddening (in a great way), and the new victory types, especially culture, considerably expand the game's options out from "go into space" and 'kill everyone." A lot of these features were apparently implemented in Civilization III, but I'm loving the shock of encountering them now.
I'm roughly 5-6 hours into my tutorial match. It doesn't represent the full game well apparently, but the fact that I'm enjoying it this much right now is a great sign.