While there are a few steps involved, once you have practiced them, you can get it set into place in just the space of a co-worker's walk to the printer & back.
Step 1: Create a picture of the desktop & set it as the wallpaper
Once you've done that, press the "Print Screen" key. On some keyboards, it is labeled PrtScn or something similar. Pressing that puts an image of the screen in the clipboard. launch Microsoft paint, choose Edit/Paste, and you should now see an image of the entire desktop. Save the image onto the hard drive, then choose File/Set as background (Centered)
Step 2: Hide all Desktop icons
Step 3: Move the taskbar
Step 4: Hide the start bar
Step 5: What to do once you've done the prank
If it's an officemate, or your sibling, or parent, and YOU are their go-to computer guy, again do nothing, as they will come to you. What you do when they come to you depends on how long you want to draw out the joke (and whether or not you can keep a straight face when you do so!). One of my standard answers when I see something broken is to wag my finger at them, and say that they need to stop visiting THOSE KINDS of web sites.
Step 6: Keyboard shortcuts
My point in bringing this up? Well, if your mark comes to you complaining that their computer is locked up, after you expound How odd it is that the mouse is working perfectly, and why won't anything respond?!?!", while you are frantically clicking on My Computer on the desktop, with your other hand, you can click Windows-E, and the Computer Explorer will come up, just like magic! You can then click into the My programs folder, and launch a program by clicking directly on the executable, and proclaim the problem fixed! Or expound on how odd it is that the program runs when you click on it, but why won't the Start button work?!
One caveat to the previous steps might be to NOT move the taskbar to the left or right side of the screen, just leave it in the location it was in. That way, with the taskbar at the bottom of the screen, just hidden, you could loudly double click on the start button (which, remember, isn't actually there), and press the Windows logo key, and the start menu will come up. You can then explain that it appears to be a faulty mouse, and they just weren't trying hard enough. You then ask them to try it, and when it won't work, you sit in front of the computer, and try it, slyly hitting the windows logo key while distracting them.
it all depends on how you want to run the scam. Whether you shout "ha-ha! Got you!" almost immediately, or whether you convince them that you need to take their box away & rebuild it, then return it to them a week later, proudly boasting that you were able to save all their documents, programs & everything, "Why, it doesn't look like it changed a bit, does it?"
if you've read this far, you have made it to the end of my first instructable; hope you enjoyed it.Thanks!