Well if it's not genetically modified super-clones, or cyborgs controlled by a man-made super computer with ever growing AI, World War III, Terr'ists, Super Viruses that turn us into zombies, or an Astroid the size of Jupiter, or Myans raising from the dead in 2012 to kill us all, or the ice caps melting and flooding everything like Waterworld and us sleeping with the fishies..... see..... It'll be man made Dinosaurs who kill us all off.
Oh.... or Oprah becoming US President.

WOOOOOOOOOOOO..... Everybody look under your chairs, I got you your own red buttons connected to a nuclear missile each.
WOOOOOOOOO.......
*waves around like a lunatic*