Hardcode mode, Normal difficulty, S-4, P-5, E-5, C-5, I-10, A-1, L-10. Good natured, Built to destroy, tagged guns, speech and repair.
Playing it on a C2Q 3GHz, 4GB ram, geforce 8800gtx 768MB win7 64 on high quality, default proposed settings. Getting quite a few CTDs, maybe once every hour, didn't happen with FO3, also saw one of those geometry bugs where an object seems to infinitely stretch out over the distance, restart.
Dialogs are much improved over fo3(what a surprise), faces and voices too, third person camera doesn't go half as far as in fo3 and aiming with it seems to work fairly well at any distance.
I play without vats and both the player and the npcs are more accurate than in fo3, because of this gunfights seem to end a lot faster.
After a couple of hours of play(and about 3 in-game days) I've had to eat and drink several times but haven't had to sleep. So far food, water and beds have been abundant and the distance between locations has been short so hardcore mode doesn't really feel like a survival mode.
Lots of skillchecks in general, but they're hard skill checks and the ones I've seen so far you can retry those checks whenever you want, this encourages the powergamer in me to hang onto those magical pants of +5 bartering in case I'm a few points short of a skill check. Skill magazines seem to follow the same idea.
Having fun so far, hope it keeps up.