First, I am noticing a LOT more conversation and topics with the people you get to speak with in places - this is a great thing since FO3's conversations often felt anemic. A lot of the dialogue is in gaining information and not "choices" but I'm enjoying it greatly. Also, I have laughed out loud quite a few times - which is rare imho in most games..... the one-liners or references have been enjoyable.
I love the new reputation system - although it's too early to see if it has a deep and lasting impact - but so far, I really like it.
The choices seem fairly black/white right now .... I had hoped for more 'grey' but we'll see as the game deepens.
I have not had any graphical slow down (have had over 15+ NPCs on screen all at once) nor crashes, nor issues of any kind with the game.
I just recently (before leaving for work) reached Primm and just started the quests there after thoroughly exploring Goodsprings.
So far, the game is just as good as I had hoped.... kudos to Obsidian so far!