Anyone used to using a UNIX-based OS like FreeBSD or Linux is familiar with X-Mouse.
In short, it changes the foreground focus (window, application or desktop) based on wherever the mouse cursor happens to be. This for many, speeds up productivity a bit by saving clicks (about a nano-second each).
To enable this in Vista, go to the Control Panel > Ease of Access Center (or press the Windows key + U). Click the link "Make the mouse easier to use" and choose "Activate a window by hovering over it with the mouse" and then Save.
Once you start moving your cursor around you'll notice the focus will change automatically after a short delay. It's not for everybody, but can be helpful when using multiple monitors. Start saving nano-seconds now :)