I'm intrigued by the "Hardcore" mode I've heard about in this game. It brings back the realism of ammunition having weight to the series, imposes a time delay between use of a Stimpak and its healing effects setting in, and keeps track of a "thirst meter," necessitating the player consume water periodically or else dehydrate (also heard something in conjunction with food consumption, but not as definitively).
I liked Fallout 3, but the immersion level was low, and something of this nature will likely go a long way to address that. Hopefully the skill system will change somewhat as well, and every character won't be a superpowered Mary Sue by the endgame.
As for Obsidian in general, I rather liked KOTOR 2 despite its faults (moral ambiguity and thought in Star Wars? I would have previously thought it impossible), though the company is developing a habit of only producing sequels for others' games (in a somewhat ironic fashion for FO:NV, of course...), though they also have Alpha Protocol on the horizon.