It seems to run fine on the family computer. The only areas where there seems to be significant slowdown for me seem to be areas where there are a lot of physics enabled objects (you wouldn't think a bunk of bottles whose only reaction to any amount simulated force is "fly across the fucking room!" would take all that much processing power but whatever), and the only real glitches I've come across in my admittedly short play time is that the Pipboy radio music (though not the announcers oddly enough) will be alternately scratchy and skippy, and also I get a redundant little error message from Vista when I exit the game telling me that "Fallout3.exe has stopped working"

Other than those (and a few other even more minor things) so far I'm impressed and satisfied. VATS combat has so far been less like bullet time with percentages attached and more like a way to make sure that you're actually attacking the thing you're trying to attack (and the animations haven't seemed overly long to me, though the pixel shaders used in it make this computer cry for a couple seconds before they load, which is a bit annoying). The interface is mostly pretty good...though using tab to enter my menu/inventory instead of esc or i will take a bit of getting used too. And so far it seems like Bethesda grokked what made the first couple games charming and have (again, so far since I'm barely past the tutorial) kept from going too far either into "ZOMG GRIMDARK SO REAL!!!111" territory or total farcicalness.
(also, holy shit, this spellchecker recognizes "grokked" as a real word WTS?!)