Disney's Toontown doesn't work with Vista. I have an 8-year-old who's seriously ticked off at his dad for upgrading to Vista.
On a more serious note, I loaded Vista Ultimate onto my now old Dell D800 laptop and it seems to work fine. It sleeps fine. The apps work fine. I like the cool graphics, mostly the cool chronometer watch/clock thingy that I can have stay up in the bar at the right. If you know what I mean by "classic mode" then you probably know what I mean when I say that I found XP's non-classic mode totally unusable. I couldn't find anything or get anything done in it. With Vista things are more informative so I don't have the immediate reaction to crank everything back to classic mode (the Start Menu, the Control Panels, the folder views, etc.)
For anti-virus I'm using MS Live OneCare. It took forever to start up in XP and it seems to take forever and a day to start up in Vista, many times reporting that there are problems, deficiencies, or errors when it's apparently only erroneously checking something about itself before giving that service a chance to start up, or that an update failed but it's only because I need to restart before it'll be installed. Because OneCare was beta through most of XP I was hoping that it was actually designed for Vista and would work much better. Annoyingly, there are some times that it still forces me to manually go to MS Update in IE and walk through that huge long procedure myself.
I do get really tired of the annoying allow/deny dialog boxes. It's so annoying that in no time at all I was trained to just approve of whatever without paying much attention to it, which, of course, totally defeats the purpose. But it just comes up way too often.
I can get my Office work done on it, but ever since I needed to ship back the original drive to Dell and format a new one myself I've never been able to get a DVD to play on this darned laptop. (I know XP didn't ship with DVD decoders natively) I was hoping with Vista I'd be able to play DVD's but all I get is sound. It's not like it's an off-brand laptop. I don't know whether to blame Dell or MS, but when I'm on a trip it sure would be nice if the ultra-premium ultra-ultimate OS did what it advertises.