1. Week 11, Kansas City Chiefs
The Bills' only opponent that prevents them from making a Super Bowl, and possibly the most hated team by Bills Mafia currently. Games against this opponent are always hyped up around the league, as they are always nail-biters.
However, that's not the main reason for the importance of this game, this game occurs before the Bills' bye. The Bills winning this game gives them some momentum going into the bye and will help them keep that momentum after the bye, which will help them face off against playoff-caliber teams for three weeks straight.
Even if the Bills were to lose one of those games in those coming weeks, it wouldn't hurt as much as if they were to lose against the Chiefs. Also depending on how the season goes, this game could be the difference on who retains the one seed in the AFC.