Here's what to watch for:
Manuel's first chance to shine. With veteran Kevin Kolb dressing but serving only as the emergency quarterback, rookie EJ Manuel has a prime opportunity to get a leg up on the quarterback battle through the rest of the preseason. The biggest question is how much he'll play. Coach Doug Marrone refused to tip his hand on Friday night, but it wouldn't be surprising to see Manuel take the first half and another rookie, Jeff Tuel, take over for the second half.
Who steps up among rookie wideouts? With Stevie Johnson (hamstring) out for at least this game, second-round pick Robert Woods and third-round pick Marquise Goodwin will get live game reps with Manuel. The Bills began their first practice of training camp with a long-ball drill; expect them to take some deep shots early on Sunday. With Brad Smith and Kevin Elliott also not expected to play due to injury, look for Chris Hogan, who has stood out thus far in camp, to see extensive action. Finally, it's worth monitoring when undrafted receiver Da'Rick Rogers enters the game; if it isn't until late, it won't help his chances of making the final cut, which is less than three weeks away.
Does Hackett put his stamp on offense early? At 33, Nathaniel Hackett is one of the younger offensive coordinators in the NFL. His up-tempo, energetic personality has left its mark on the Bills' offense, which aims to wear down defenses with a speed-oriented, no-huddle approach. But if Hackett reveals too much of his strategy in preseason contests, it will give opponents an opportunity to dissect the scheme on film, so expect something more toned-down on Sunday. With Manuel seeing his first game action in the NFL, it may be best to slow the offense down until he gets comfortable.
Where does the pass rush come from? Marrone said Friday that defensive end Mario Williams (foot) will be a game-time decision. At this point in the preseason, it seems unlikely the Bills would risk putting Williams on the field. After Williams, there is a significant drop-off among proven pass-rushers, something that has arguably flown under the radar in training camp. The Bills seem to be expecting big things out of Jerry Hughes, who will be returning to Indianapolis, where he was a former first-round pick. The team also appears high on Jamie Blatnick, who should see significant playing time Sunday. The first time the Colts are in a third-and-long situation, it will be worth noting who is on the field and what pressure they generate against an improved Colts offensive line.
Left guard another battle to monitor: Beyond the obvious competition at quarterback, the Bills have an open left guard spot that is far from being decided. The focus will be less on who starts -- it could be Colin Brown, Doug Legursky, or someone else -- and more on how they perform when in the game. Marrone hasn't seemed satisfied with the battle so far and has been working closely with the offensive line in practice. You can bet that he will be taking a close look at the film for that position on Monday morning.