A Cast Member Dies
As is the case with any workplace, the untimely death of a cast member creates a dark cloud. Their aren't millions of people watching you plug numbers into spreadsheets as you grieve, though. If a character's part is small enough, or if they're on a show where death is somewhat common, like police procedural Hill Street Blues, a character death won't necessarily sink a show.
Still, there are cases proving the opposite to be true. Eight Simple Rules, NewsRadio, and the recently departed Buckwild are just a few examples of shows that couldn't withstand that passing of a key cast member.