Fatigue set in largely because the offense started going into 3 and out mode like it did last season at the wrong time. Manning cut the lead to 10, and on their opening play, the offense comes out in an empty backfield formation, when it made absolutely no sense in any way to be doing that. The goal should have been to run clock, they had been running on the Colts all day, and they were playing against a defense that thrives on teams not using the run.
He played well, but Brady harping on how he's "more comfortable" in the shotgun ever since PollardGate is a cause for concern if it doesn't stop. Once Manning cut the lead to 10 their next drive they should have come out in the ace formation with Crumpler and Gronk at tight end, and they should have used play action a few times. Crumpler and Gronk were blocking Mathis and Freeney without any help on running plays, that front would have been most advantageous at the time.