While the season opener is a tough one against a potentially ranked conference foe, week 2 will be the type of game we have not had in some time. Unless you are dumb enough to schedule North Dakota State there is no valid excuse for a power 5 team to ever lose to an FCS team. The difference in talent, resources, and everything is just too great. Still, it does happen from time to time. Last season four Power 5 teams (Arizona, Florida State, Washington, and Vanderbilt) lost their FCS cupcake games.
Michigan is the most famous Big Ten example, but Northwestern, Iowa, Indiana, Minnesota, and Rutgers have all had it happen to them.