What i'm mostly looking forward to in this is:
Excessive gore. (More then the previous one)
Nudity.
More modern guns.

The reputation system.
Companion quests.

I'm looking foward to hitting every ghoul I see and to hopefully find one that will utter those famous words.

Looking forward to ghoul hookers and super mutant hookers.  And albino radscorpion hookers.

I'm just happy that it's more Fallout. I was nervous that they were going to change a lot from Fallout 3, but from the looks of it they haven't.
 
Oh and maybe the landscape will be a little less bland.

electricity and shitty graphics still

" The reputation system. Companion quests. "

" @Alphiehyr: You're thinking of the Karma system. I'm talking about the reputation system. "

More fallout

Killing Easy Pete and stealing his hat.

Exploration and the radio, i loved the music in the first game.

Since it's in Vegas, I hope there's going to be a large variety of outfits.

More cruelty, or a better script. Remeber when you blew up megaton, came back to see your carnage, and there's Moira Brown- completely
disfigured, yet happy as a clam? It would have been awesome if she was utterly distraut- trying to force tears from her cauterized lacrimal ducts, screaming, "Why? Why?" And then tell her that you did it for no reason whatsoever. Then decide whether to put her out of her misery...or leave her to rot.

Honestly I'm justing looking forward to what is essentially more fallout 3, you can only go through the last games and it's expansions so many times before you need something fresh and I still have my chem shakes telling me to play more fallout.

A Larger set of assault rifles.

Proper dialogue and non asinine storyline.
Hopefully Obsidian will come through on their promises.

More Fallout humor.

the MEC Gauss minigun.

I'd like to see mutated celebrities like Frank Sinatra or Elvis Presley. Some new guns would be nice. And maybe a slightly longer campaign?

I'm most excited about seeing what the strip will be like.

A new DOG

An ending that isn't compromised by the fact that I should be able to avoid doing something incredibly hazardous when someone else much more suited to the job is standing right beside me, but I'm prevented from ever making such a common-sense suggestion.