They weren't kidding about the optimization from what I see. My framerate tended to take a serious dive around crowds and the Old Mormon Fort but no longer, very nice. That said, I still encounter a bug where mousing into Cass's inventory (not opening it, just mousing over her items) causes the game to crash. Not game-breaking, I just use ED-E for storage instead, but weird.
Also, Dutch, have you tried unchecking all mods? I had a similar problem for Freeside and Rivet City way back, and in both cases it was solved. Just unckeck all mods, enter, recheck them, problem never happened again with no patch in between.