Really not a big surprise. The Bills defense was able to win the first two games, but they could not against Rivers. This game the Bills needed Manuel to be more than a game manager, and he was not even close to being up to the task. This may be the recipe for this season anyway. If the Bills D can dominate, the Bills have a very good chance of winning. If they cannot, the Bills chances of winning become very poor.
Hopefully Manuel will become a good NFL QB and will be able to win some games. Based on his collegiate career and his NFL career to date, I tend to doubt it. But hopefully the brain trust saw something in Manuel that will make me change my mind.