The current issue of MacAddict has a whole section on April Fool's jokes, mostly for Macs but I'll mention the Wintel ones.
The first suggests you go into the conrol panel for the mouse and switch the settings for the buttons. Kind of lame but might annoy the low-level user.
Second, if they are using Windows ME, 98 or 95 you can download
this file which will allow you to change the Blue Screen of Death to another color.
At work one year I put an extension that reversed letters on my principal's machine. He thought it was another language.
I also put the extension that creates a bouncing mouse cursor in another teacher's machine. The kids in her class had a great time playing with it.