I place it surprisingly high:
1. I will always place Wide-right as the ultimate Bills heartbreaker, it seems those two or three feet separating the football and the goal post will be as close as the bills ever get to a Super Bowl victory.
2. Music City "miracle."
3. 1966 AFL Championship game. The Bills were very good in the years leading up to the first Super Bowl, unfortunately they fell just short when it mattered the most for them. They could've played in the first Super Bowl against the Packers. Disclaimer: I wasn't alive, but the thought of a Good Bills team coming up just short the year it mattered most really seemed to set a tone that sticks with this team to this day.
4. Leodis' fumble against the Pats. It was the Pats, at the time I felt like the Bills could turn the corner with that game, some asshats sprayed his lawn, Tom Brady was smiling and I don't like that. Heartbreaking.
5. Falcons in Toronto. Say what you will about it being Doug Marrone's first season, he inherited a better team than either Gailey or Jauron. The fact that the Bills could've put themselves into a prime position for a playoff run and still allowed the losing mentality or curse or hex or whatever to bring them down in this fashion is heartbreaking. Poor officiating, not one but two fumbles to lose, in overtime, in Toronto, removing all hope of a playoff birth after 14 years. I'm afraid Marrone has some work to do, it's like Bills players, fans and coaches even the refs EXPECT something bad to happen, so it does.
I rank it slightly higher than these two, which is saying something because I hated these games pretty bad.
6. Jaguars win the game on a last ditch pass to the endzone, first game of the season sets the tone for the whole year and apparently years to come. I was in college and I talked a lot of crap leading up to this game, I fully (see: naively) expected the Bills to be good that year. The worst part is the receiver didn't get two feet down, it was ruled that he was forced out of bounds, then a few years later the NFL gets rid of that crappy rule.
7. Cowboys Monday Night game when the Bills weren't ready for the onside kick for some reason. Romo for 5 INT's and the win. Yuck.
I was going to go to ten, but this is depressing, I need a drink.
Anyone know a witch doctor?