One issue is that the average fan seems to have a major problem with the game becoming less violent. The NFL's best interest obviously involves a reduction in injuries, but they (understandably) fear a harsh reaction from fans for any rule changes.
While I understand the innate desire to resist change, the game has been evolving since its inception. Back in the day, I'm sure some people thought the forward pass would ruin the game.
My first change? Do away with the 3-point stance. This would work wonders with the sub-concussive impact problem.