My favorite one that I've pulled was on an office manager. (Mannyy years ago) She knew absolutely nothing about computers and even the simplest of computer stuff confused her.
Early in the morning before she came in..I set different "noises" to happen with a whole bunch of her keys on the keyboard.
space bar= dog barking
enter= clap of lightening
the "S" key= a scream
and so on....
It was great!! She didn't have a clue that I'd done it. I was watching her from my desk as she looked BEHIND the monitor, looked at her mouse, lifted things.. She couldn't figure it out and thought she could just "work with those silly noises". But about 3 hours later, she was in a bad mood. She came and asked me to "look at her computer" and figure out what she had done wrong to it.
I ended up telling her...we laughed...now it's in "practical joke history".