In my opinion, the greatest threat to the future of professional football is the potential of a declining talent pool.
As the scientific understanding of head injuries in football is brought to the spotlight, more and more athletically talented children will be pushed toward alternative sports by their parents. Even if this phenomenon occurs at a relatively low percentage, the long term ramifications are considerable and very real.
This is one of the more significant reasons why Goodell is making such a strong push toward a "safer" league. It's about perception as much as it is about reality, and the NFL does not want to see tomorrow's best athletes start to get funneled into baseball, basketball, golf, soccer, etc.