On a gentoo box, doing an `emerge -u world` a week after finishing building it.
There goes two weeks of work (slow box, slow compiles).
Second would have to be a bad crimp on an ethernet cable bending a connecter pin in my dsl modem. Put a good cable in there and that wouldn't work 'cause of the bent connector! A half a day of downtime later as well as a smack to the forehead, and I get high-speed internet again
