The one major downside is the sheer number of times I have had to reboot. Every little thing seems to require a reboot, especially compared to Linux and Mac OS X, that only need a reboot once in a blue moon. I've also run into some odd window focus issues that drove me mad until I rebooted (of course), but I can see how someone well-versed in the Windows reboot trend from years of Windows 98, 2000, and XP would think that Vista hardly ever needs to reboot, and count that as a positive step.
At the moment, I have a half-dozen SSH sessions running using Private Shell (which I've found to be a very decent Windows SSH client), FireFox, Thunderbird, Microsoft Word, Ecto for Windows, Outlook, Pidgin, and six widgets, including the XM Radio widget tuned to Beyond Jazz. I'm also running Nokia's PC Suite applet, and another dozen tray apps. The CPU load is around 5%, 26% of the 8GB RAM in use (2095MB).
The infamous UAC warnings have been toned down somewhat, but it's very annoying when they do appear, as they blank both screens for an instant when they are invoked, and again when they are dismissed. I'm not sure if that's a driver issue or not -- I'm using nVidia's drivers, so I'd hope that wasn't the issue. I've also had some applications vanish from the taskbar, yet still be running (and accessible from the Task Manager), and some other relatively minor nonsense. The new Start menu is really annoying, oh, and the lack of middle-button pasting (a la X11) is driving me batty.
Other than those issues, I've been pleasantly surprised so far. Now let's see if I can last the week.