So far, F3 really nails the Fallout feel. Especially the opening "character growth" / character creation sequence - that was really well done.
A quick comment on the organic character generation, though. Although it's fun to see what kind of character gets spat out, players may not get what they ultimately want. I tried not to "game" the aptitude test sequence, and did get a character that was pretty much want I was hoping for, barring one weirdly-placed skill focus point. Wisely, Bethesda allows you to tweak your three skill foci though, so all was well. (I think the original Fallout let you do a final tweak too.)
I'm not fond of the real time melee combat - the control feels muddy and mushy - maybe even drunken. Note that this comment is based on solely on baseball bat vs. nightstick scuffles in the cramped quarters of Vault 101 - hopefully melee is less annoying out in the open wasteland. I found this fact strange, because melee in Oblivion had seemed a bit more precise. (That said, my Oblivion character was an archery specialist, so I didn't do as much sword hackery as pointy-stick-launching.) Hopefully, the VATS system will make up for the mushy-melee shortfall, but my jury is still out on VATS.
So far I've played through the (extensive) opening sequence, left the vault, and after a quick scout around the surrounding landscape, made my way to the first town (Megaton).
I'm enjoying the characters, atmosphere, and dialogue so far. The Oblivion-engine facial models though, are still creepy. They are stiff and lifeless - especially compared to Mass Effect's exemplary showing in that area. I find the effect jarring, especially paired with the excellent F3 voice acting and dialogue writing. Given that older games (Half Life 2 comes to mind) have done a much better job with facial animations, Fallout 3 character faces end up looking very dated.
One last early observation - I can't seem to access a description blurb of the items present in Container or Barter windows. Sure, "Sawed-off Shotgun" is self-explanatory, but WTF is a "Schematic: Shishkebab"??
More after additional play time.