Your cities with the cultural borders now work a lot more like an actual country, and not just a collection of city states. This is nice...I was always less then impressed with having cities and colonies scattered across the globe with no detrimental value. The changes to the Trade system require networks of highways and roads/harbors to cultivate commerce, so it's in your best interestes to keep those things close together...Finally, we're dealing with an entire culture instead of just city-states. And if you're a real monster, you can use the gigantic maps and pull up all 16 civilizations.
Armies can be more decentralized, and wonders of the world are useful, but there are fewer "Killer" wonders that can completely upset the balance of the game. For example, in the previous game, The Sistine Chapel created a cathedral in every city, which made it a prime target for large civilizations...now the advancement simply increases the effects of cathedrals, which forces each city to get off it's butt and develop it's own resources.
Espionage and Trade have been abstracted. Trade and Commerce are now dependant on roads and resources and money comes from trading with other civilizations. And no more of that horribly unrealistic plan of sending the spy in to destroy city walls before the invasion. (I mean, come on...destroy city walls?)
My favorite new aspect is the cultural assimilation of other cities. For example, if you have a strong cultural identity (basically, borders) - and you are close to cities that don't...they may rebel and join your side...much in the way that several cities/territories that once belonged to Mexico joined up with the U.S.
I haven't finished a game yet...I made the mistake of getting my spies busted one too many times...First one country declared war on me...then I attacked and a second one with a Mutual Aggression Pact came at me. Then a couple of them started trade embargos against me, then a couple of turns later the other two guys around me declared war, just like Russia and Germany did with Poland. I got beat up pretty bad and chalked it up to a learning experience...
I have a couple of minor issues....most of the menus are relocated and are kinda hard to find. And I never liked those advisors in the first couple of games..and now they're intergrated...but overall, it's been a long time since I've been pleased with a game like this...This is the game you feel like telling the /. community is worth buying a copy of Win98 for.