When Goldeneyes Silverhand Dactylos dies. Perhaps the most awesomely cool character I had ever read about, with an amazing backstory and a friggin' cyborg to boot... and he doesn't survive more than three pages. Thanks for that kick in the balls, Pratchett!
The film version starts with Rincewind being expelled from Unseen University, and attempting to jump into the River Ankh. Fortunately, it doesn't stick as soon as he's saved by ship cargo being unloaded and spots The Luggage.