The knee-jerk reaction is to go with a prank that will be over with quickly. That's amateur hour, though. What you need to do is to make your friends terrified of life.
Firstly, this involves an incredible amount of dedication. You need to keep this up the whole semester. They'll be expecting you to exact revenge, but they won't know it's you. This way, you'll have a semester free from these pranks while also executing a brilliant revenge.
Start it small. Slip a vial of different colored liquids into their bags throughout a week. Mark them with a radioactive sticker and seal them tightly. Give yourself one, too. You need to seem like you're thrown into the mix as well--it will avoid suspicion.
Next, plant some anonymous notes along the lines of, "We know you have it. You have one week to return it unharmed." Get somebody else to write it so your handwriting isn't recognized. It's best to hide these in text books or laptop bags--where they'll be carrying it with them but won't be immediately obvious that it was you. Also get notes to be a counter, like, "Your government appreciates you cooperation in keeping this precious cargo safe."
Next, convince somebody that they don't know (money may be involved) to stare and follow them for an appreciable part of the day. Tell him to keep his distance and wear a trench coat. Also, make sure he talks into his sleeve at regular intervals. If your friends confront him, have him yell into his sleeve, "I'VE BEEN COMPROMISED!" and run the frack away.
Two weeks later, get a different person to sit on a bench wearing a suit and sunglasses on a path that they typically walk by. When they pass, have the person say audibly into his coat, "Got a visual. Heading toward checkpoint Bravo. Shoot to kill."
During this while, use your knowledge of families against them. Make calls to their folks while using a voice changer and an anonymous line (or block your number). Ask for whoever the kid is. Tell them to pass along the message that Boris is looking for them. It helps if all of this is in a passable Russian accent. People are still afraid of the Russians--I don't know why.
Keep leaving random notes in their belongings. Make it seem that whatever they are supposedly in possession of is potentially harmful to their health but vital for national security. Tell them that the vials need to be between 40F and 50F until further notice. Have a friend try to tell them that they should be freezing juice pops, not refrigerating them--and then helpfully put a vial in the freezer. Enjoy it as they freak the frack out.
Have "the CIA" pass along a note that they will recover the vials the last week of graduation. Give each person a rendezvous in the middle of fracking nowhere. Tell them to leave their cell phones at home--they don't want to be traced.
Leave a note in the spot that says, "Your mission has been compromised. Good night and good luck." For bonus points, hide in the woods with a cap gun and start firing--watch them bolt the frack out of there shitting their pants.
They will never frack with you again.