Here's my wishlist:
1. In the last five minutes of the game, when the team that's in the lead has possession, the clock should stop on any play where they fail to gain yardage. They can't just kneel down to run out the clock, but have to accomplish something, even if it's just gaining one yard. And the defense would have the opportunity to stop them and get the ball back. (This is something the Arena league did, and it kept games exciting until the end.)
2. Replace coin flips with an opening scramble. A player from each team would line up 30 yards from the ball. The ref blows a whistle, and whoever gets possession of the ball wins the equivalent of the opening coin flip. Since it's skill instead of luck, it would be reasonable to let them choose both possession and direction. (This was one of the few good ideas the XFL came up with.)
3. College style overtime rules.
4. Make everything reviewable, including penalties and judgment calls. (Still using the current red flag instant replay rules.) Even if it's a judgment call, the ref will have better judgment with the help of 12 angles and slow motion. (I saw this suggestion in an interview with one of the mucky-mucks at Football Outsiders.)
Some other changes that I'm not sure about, but would be interesting to see play-tested in an R&D setting.
A. Changes to the way penalties work. Like maybe someone who commits a penalty has to sit out a play. This could be done with a substitute, or with the more radical notion of forcing the team to play with 10 guys. If you allow a substitute to replace the penalized player, it would make sense to do that even if the penalty is declined.
B. Field goals could be worth different amounts based on distance.
C. Get rid of extra points. Either make touchdowns worth 7, or make teams go for two after every touchdown.
What do ye think?