Take a screenshot of someones desktop and set it as their background. Remove all the icons. Then, when they go to click the shortcuts, nothing will happen.
Keyboard and Mouse switcheroo
This only works on PS/2 keyboards and mice- just go in the back of the computer and switch the keyboard and mouse. An error message will come up saying "Keyboard not present. Press F11 to continue". Very confusing to the victim.
Download this application. Run the .exe. It enters in a random key every minute. To undo it, just restart your computer.
Remember clippy, that annoying-ass little paper clip that says useless shit every time you opened up word? Download it here. Then customize it to say whatever you want. Imagine your victim's reaction to a swearing paperclip.
Custom Error Messages
Go to notepad and input the following text;
X = MsgBox("Box Text", ,"Box Title")
Substitute whatever you want the error to say for Box Text and whatever you want the title to be for Box Title. Then save it as whatever you want with a file extension of .vbs. Make a whole bunch of these and save them into C:\Documents and Settings\(Username)\Start Menu\Programs\Startup. Then, when the victim starts up their computer, they'll get a whole bunch of errors. Great prank.
Internet Explorer Shutdown Prank
Note: you can do this with any program. If you really want to piss your victim off, do it to all of their shortcuts on their desktop. More pranks later.