With the CAVEAT that balance, bugs and AI needs further fixing and tweaking, I like Civ5 a lot:
* Science is no longer based on Commerce.
* Border growth.
* Science/Commerce/Culture/Espionage slider is gone, which was an oversimplified mess imo.
* Social Policies. I can no longer switch in and out of governments as needed, I have to plan ahead, giving my civ a sense of direction and character.
* Stack of Doom is removed in favor of tactical combat, 1 unit per tile/hexes.
* Limited Strategical Resources.
* City States. Do I invade or do I befriend? Do I carry out their requests?
* Global Happiness/Golden Ages/Culture system, allowing small empires to win.
* Unique Leader abilities.
* Modest tile yield. No more OP starting locations.
I'm sure there's more, but those are off the top of my head.
There are several things that need to get fixed/balanced, especially with the AI/diplomacy (as always

) but I do enjoy Civ5 quite a bit!