The London game, specifically the let down of the Defense after the Bils had rallied back to take the lead, then allowing Jacksonville to march down the field and score the winning TD.
It was really the clincher in the evidence that this defense was bad, and just didn't have it. If the Bills hang on to win that game, they would still be in the playoff hunt today. And, it would have been a huge momentum changer for the season.
Yes, until they out him on the ring of honor, or something, the curse will continue.