You say that upsets matter and point to USC and Oregon State, but obviously Florida losing to Mississippi at home didn't matter.
Bottom line is that having a playoff wouldn't cheapen the regular season like basketball's regular season because the standard to make the playoffs would be pretty high, even if it was as large as a 16 team playoff. Yes, losing one game wouldn't kill the season, but then again, you wouldn't have teams like USC, Texas, Penn State, Texas Tech and Alabama, all of which have some argument as to why they are as qualified as the teams that are there.
The answer is to find a way that would still allow for the cash-cow bowl system to co-exist. All bowl games but one are essentially meaningless exhibitions anyway so I don't see how this can't be achieved.