How to mess up a PC running Windows 7?

A few major problems for you,

• In bios disable the processors L2 cache - Machine crawls
• Windows+break-->advanced system settings --> hardware tab --> Device Manager, right click disable mouse (make sure you can get here with just your keyboard so you can undo this!)
• ctrl+alt + Arrow key - on some graphics cards this rotates the screen. (usually with no method of undoing this unless you know this shortcut)
• Make a floppy boot disc/usb Key/CD Rom, pop it in the floppy drive and ensure its set to first in the boot order in bios (bonus points for removing the hdd from boot list and creating all 3 boot discs with a different os on each so they fix one then get the next!)
• Use a partitioning tool to shrink the hdd partition to a few mb more than is currently in use
• Do the opposite and fill up available space with multiple copies of large files. Combined with a startup script to start the copies would keep the hard drive filled if they first attempted cleanup by deleting files.

And a few irritations to garnish the pc with

• If it had internet access - Open Internet Properties --> connections Tab -->Lan Settings, Check use a proxy server, set the address to 127.0.0.1 (prevents them googling for solutions :P)
• Right click on desktop - View - uncheck show desktop icons (irritating but not tough to fix)
• sticky tape on the bottom of the mouse can disrupt the laser stopping the mouse working (couple this with the major disabling of the mouse in device manager to add confusion).
• if the connectors are ps2, swap the mouse and keyboard, obvious if you're used to hardware but passes a quick glance from a noob
• In word Office button -->Word Options --> proofing --> AutoCorrect Options --> add a few entries for common words, subtlety is your friend, is --> was the --> teh etc (2k7 instructions but can be done via different route in most versions)

Reverse the steps to undo the problems and ask in comments if you have trouble!

Edit - as we may have had our beastly BIOS tricks taken from us here's a couple more windows based ones

Put the shutdown command into autoexec.bat Command syntax here (you've talked about putting similar functionality in the startup folder, so this should confuse em by doing the same thing from a different spot)

Fork bomb! Create a .bat file containing the following text and make it autorun (either call from autoexec.bat or drop the .bat in startup folder)

:s
start %0
goto s

This will spawn huge numbers of processes untill the machine grinds to a halt (The code is untested but looks viable)

Create a mouse cursor theme where the arrow tip is NOT at mouse position.

This should be puzzling enough.

Change the keyboard layout to "Dvorak" or some other obscure non-English setting. They'll probably figure it out fairly quickly but it will still be really obnoxious to fix. In advance, you can write down the key combinations needed to switch back.