Interesting facts:
You're not a vault dweller!
Takes place 3 years after F3, 40 years after F2.
New Vegas wasn't hit by as many nukes as Washington so it should have peachier weather!
VATS mode now has special melee attacks!
If you missed the geckos from Fallout 2, they're baaaaack
There's still karma, but there's also a reputation bar because there are three major factions in New Vegas.
Your choice of skills should have more impact on dialogue.
You can command your followers now to a limited degree.
It uses the same engine as Fallout 3 but is being developed by Obsidian (KOTOR 2, NWN2). Interesting story: Obsidian is made up of a lot of the same people who made Fallout 1 and 2 as well as Planescape: Torment, known as Black Isle Studios.
INTERESTING STUFF.