From an old thread about April Fool's Day pranks on a roommate or friend:
download a shitload of kiddie porn onto his laptop, then just sit back and wait for the Feds......
feed his girlfriend a bunch of roofies, then fuck the shit out of her while filming the whole thing and post it on his favorite porn site. Do the same thing to his mom and his sister.
Get him so violently ill that he's bed-ridden for a week straight by putting a little bit of shit in his food, hide his cellphone and laptop and sabotage his car engine so he's essentially cut off from the world for a few days. When people ask where he's at, say you haven't seen him in a week or so, then bribe someone at the local newspaper to put his obituary in the paper every day until all his friends are convinced he's dead.
If he's an animal lover, go down to the local Humane Society and get a dog they're about to put down. Get a nail gun and nail the fucking thing to his bedroom door and let it bleed out there.
Feed him roofies and take him to a gay bar, then just leave him there. He'll wake up the next day with an asshole like a jar of mayonnaise.
Is he in school somewhere? Get his student ID# and his SS# and then have him "drop out".
Go into his work. Approach his boss and ask him if it's possible to attach your buddy's wages because he's owed you $800 for some smack you fronted him months ago and he won't return your phone calls.
Wake him up every morning with a brick to the face.
Put a drop or two of Visine in his drink. Do this every single day for as long as you know him. When he complains that his stomach is totally fucked and he keeps shitting himself, give him some Pepto-Bismol and act really sympathetic. Don't tell him that you diluted the Pepto with a bunch of Maalox.
When he leaves for work in the morning, hide down the street and when he drives by, throw a bowling ball through his windshield. When he returns home from work (assuming he hasn't had the windshield replaced) throw a fucking Molotov cocktail into his car.