By assigning point values to field position, down, distance and time, we can estimate the real point impact of a play. Expected point values increase as team's get closer to the end zone and decrease as the end of the half approaches and as they use up downs. By this measure, the most expected points come from the opponent's 1 yard line, first down, in the first 29 minutes of the half.
I also adjust for the expected points for the opposing team in their next possession. Teams that are pinned deep in their own territory tend to give up more points on the subsequent possession than teams that are forced to punt around midfield.
With that in mind, the most possible points a single play could cost a team is 14 - if the team with the ball was expected to score 7 in their possession and allow 0 in the next possession, but instead gives up a touchdown on a turnover. Practically speaking the most points a team can lose on one play is closer to 12 because no team is ever expected to score 7 and never expected to allow 0.
So, the worst possible play is a turnover at the 1 yard line with about 1 minute left that is returned for a touchdown. That is, more or less, what happened to Army in their 2010 game against Navy. Trent Steelman lost the ball on the 2 yard line and then watched Wyatt Middleton return it 98 yards for a touchdown. That was the worst play in FBS football over the past 5 years and we can only assume it was one of the worst plays in college football history.
The star of this list is UTEP's Quintin Demps, who returned two interceptions 100 yards for touchdowns.