Played from 2 till 430 since I got it. It does indeed continue Desmond's story, and in one of the first scenes with Desmond it actually answered one of my biggest questions from 2. So far, I'd say I've spent more time as Desmond, but it feels like I just entered the meat of Ezio's story so I think I got quite a bit of animus coming my way. They added replay for seperate missions, so that's a big plus. Lucy also told me I could leave the animus whenever I please, but I don't know if it'll offer anything knew other than the times I expect you'll be pulled out by the story. Quite a few noticable combat additons, my favorite being it's faster. Feels more like you're an assassin and the people you're fighting WANT YOU DEAD, they're not going to take turns going at you. Animation is very fluent in combat, Ezio moves very smoothly between kills and it looks very realistic.
Wandering if it reads your assassins creed save to determine your loadout of weapons and armor at the beginning though. I started with Altair's armor, though I didn't get a good look at my weapons.
Spoiler They strip you of them after a while though, so you can get that sense of progression I'm sure.
Haven't tried multiplayer yet, that can wait until I finish the story mode.