A one-word answer:
A more detailed answer:
1. Head shots will be taken out of the game - completely.
2. Safeties will have to be able to cover slot receivers -- secondaries will look more like four corners than two safeties and two corners as now (in part because safeties will not be able to punish people over the middle due to head shots rule changes).
3. Linebackers will be either edge rusher guys (like Aldon Smith) or pass coverage guys (like Derrick Brooks used to be, Luke Kuechly is now). Read and react guys are done - they either play downhill, or in coverage. The 260 pound downhill middle linebacker who plays in a phone booth but not sideline to sideline will be extinct.
4. Because of spread offenses and read-option offenses, shutdown corners will be devalued, as most teams will operate out of three WR sets with athletic tight ends as a fourth pass catching option.
5. The golden age of athletic tight ends will only continue. You are going to see the TE become the #1 pass catching option on about a third of NFL clubs (Gronk, Graham, Witten, Gates... etc.)
6. "Pocket passer" will become a pejorative term; the QB of the future will need to attack the defense via run and pass like RG3, Russell Wilson, Cam Newton, Andrew Luck, etc. Championships are NOT going to be won ONLY from the pocket in the future.
7. Great pass rushers and quarterbacks will be the two most highly paid positions on the field
8. Running backs will continue to be devalued; everything is about the passing game now.
9. Defensive tackles are going to get smaller, becoming 280-310 pound agile, one-gap players as opposed to nose tackles and big run stuffing tackles.
10. Two types of wideouts will thrive -- small and fast guys (Tavon Austin types), and giants (6-3 and up). The 6-0, 200 pound receiver is going to be de-emphasized for size edgecraft at both ends of the WR position.
11. Special teams may not exist in 10 years due to injury concerns. Possession may just change with 40 yards for punts kickoffs for field position difference with no returners, etc.
12. I think replay is going to be abolished.
13. The use of live animals as mascots will cease. Cheerleaders will be more like gymnasts and will wear more respectable attire.
14. The Redskins will NOT be called the Redskins.
15. Sideline reporters will be banned (Ok, that's a hope on my part).
16. All players will be mic'ed up on seven second-delay, with helmet cams on the front of all helmets (sort of what NASCAR did putting cameras in the dashboard of every car)
17. Coaches will text plays into the QB on his wristband watch (sponsored by Nike Play).
18. One team will hire a supercomputer to call the plays and text them into the QB, based on quants drilling into data.
19. Extra points will be eliminated (kicking). Go for two will become go for one.
20. Teams will wear sponsor decals on their uniforms; at least five teams will be owned by companies.
21. Toronto, London, Tokyo, and Berlin will have NFL teams (all owned by Qatar).
22. Roger Goodell will retire and be replaced by ... Commissioner Ray Lewis. Kidding. It'll be Condi Rice.
23. The Bills still will not have won a Super Bowl.
24. At least 10 minorities will be GMs and another 10 will be Head Coaches -- so unlike today.
25. Some team will have the first female GM.More questions on NFL: