There seem to be two primary pathways to upsets in NCAA football.
One is early in the season because programs have not been properly ranked yet -- Florida State finished 5-7 last year, so it's hard to call any of their losses a true upset. Appalachian State over Michigan is the biggest true upset that I can think of since Michigan ended up being pretty good in 2007. It's pretty rare though...most of the time those early season games are little more than preseason warmups in front of half-empty stadiums, and it's not even a big deal if you lose since it doesn't factor into conference standings.
The other scenario is a highly ranked team losing on the road in conference play. We see this all the time in the Big Ten and many of my favorite Big Ten moments have been Wisconsin, Iowa, Purdue, etc beating Ohio State, fans storming the field, celebrations that go through the night, and so on. That's the true beauty of college football.
Conference realignment is likely to increase that second type of upset, which might be the biggest benefit to all of this.
I feel like one of the arguments for an 8- or 12-team playoff field was to generate more high-stakes upsets, but whether or not that would actually work was kind of an unknown. More than anything I just want to move away from neutral site games, which I hope these big geographic gaps will help with. Wisconsin vs. Notre Dame in Chicago was underwhelming (it's too bad Lambeau was canceled but even that would have been no better than playing in Madison). Wisconsin@UCLA at the Rose Bowl? Sign me up for that one. And please, please, please make the SEC teams come north for first-round playoff games.