Why does everyone assume 16 team leagues? There are a lot of leagues that are there or have approached that for some time and the reasons for going big have been slipping away. I think by the time things blow up - if they do - no one will really want to have leagues that big. A 16 team league really isn't a league at all. The divisions are really separate leagues with agreements for interleague play.
I have always felt 11 team conferences were the optimum- play 10 games against teams in your conference and 2 pre-conference games. So IMO the Big 12 at 10 teams is closest.
I am hopeful that at some point college presidents among the Big 5 get smart and negotiate the college football TV contract as a single body- similar to the NFL. Having 6 or 7 conferences with 11 teams each and regional based would make for a great fan experience. Then have each conference regular season champion make an 8 team National Championship playoff- with 1 or 2 other teams selected by poll.