It's next to impossible. Requires something that doesn't exist here. But, killing an Original (should it happen) will also kill every vampire descended from that bloodline. If you killed Nik, you would also kill Katherine, the Salvatores, Caroline and, if he was here, Tyler Lockwood. If you killed Elijah, you would also kill Lexi and her boyfriend. Just in case anyone here decides to try to kill us on principle or something, they'd also be murdering others.
Admittedly, I don't have any descendents that people seem to care about so I'm basically relying on the fact I'm pretty.