Completing "The Power of the Atom" quest by destroying the town of Megaton will max out your negative Karma instantly (assuming you didn't have any good karma to start with, though even if you did, you won't be very far from the negative extreme).
1) Go to the town of Megaton. Head into Moriarty's Saloon, which is on the other side of the town from the entrance.
2) Seek out a Mister Burke, who should be seated in a chair to the right of the saloon entrance. Agree with his proposition; he will give you a Fusion Pulse Charge.
3) Go down into the center of Megaton; you should see a large, undetonated nuclear bomb as well as several people huddled around it. Stick the Fusion Pulse Charge on the bomb. (25 Explosives required)
4) Exit Megaton and head due southwest to Tenpenny Tower, which is a tall apartment complex. (The location should be given on your map.)
5) Activate the intercom near the outside gates of Tenpenny, and the guard will eagerly let you in. Enter Tenpenny Tower.
6) Enter the elevator behind the receptionist's desk. Upon exiting the elevator, you should see a security guard and a door to your left. Talk to the security guard, and he should open the door. Go in this room, turn right, and enter the new elevator, which will lead to the very top of Tenpenny Tower.
7) You are now ready to talk to Mister Burke again. Do so, and you should see a gray suitcase-esque object sitting on the Tenpenny Tower balcony railing. Activate this object; this is the detonator for Megaton's bomb. You will see an enormous explosion, and your Karma will plummet.
Alternatively, kill, steal and if you have the cannibal and/or contract killer perks, eat the corpses and take their ears to littlehorn. This takes longer though.