I'm only going for matches I've been to.
Luton relegation 1983. At the time, it really was the end of the world.
Losing 3-0 at home to Oxford, mid to late 80s, god we were shit that day.
Losing 5-0 at Charlton (at Selhurst Park), mid to late 80s xmas/new year fixture, if ever a team was lucky to get nil it was us that day.
When West Ham knocked us out of the FA Cup about 12 years ago. It was a home replay for a place in the semi final, where we would have faced Middlesbrough. I think that's the most disappointed I've ever been at full time.
But it doesn't half make you appreciate the good times.