So I've come up with a plot. Feel free to share your Opinions and Ideas.

A non-zombie-creating, regular virus that just kills people.

Good old nuclear war.

Giant solar flare burns everyone to a crisp (except, you know, your characters, who were somewhere safe).

Not quite so giant solar flare fries all electronics and modern humans are too stupid to live without our gadgets.

Global warming somehow causes an ice age instead, but real quick-like.

Pet monkey revolution.

Trapper-keeper Skynet.

Asteroid like the one what killed the dinosaurs 65,000,000 years ago.

Flood like the one what killed the dinosaurs 4,359 years ago.

The Rapture, Sea of Blood, Whore of Babylon, Mark of the Beast, etc., etc. (you know, the Apocalypse).

Cubs win the World Series; Hell freezes over.

Mass confusion leads to a lot of people dying, and the majority of the world's infrastructure crumbles pretty quickly because no one knows how to keep it running.