The major one is the huge issue of injury, specifically concussions that were ignored for years. The knowledge and frequency of head injuries occurring to players at all levels from Pop Warner to the NFL has caused many parents to guide their sons away from the game to safer sports. So the talent base will eventually diminish although the allure of big time $$ has overcome many better sensibilities. I expect the NFL to eventually pay billions to address and correct it.
As ticket and concession prices continue to escalate it has cut the affordability of the everyday working man to go to the games. Further, as others have noted, there are other ways of watching games without paying the steep rates for viewing that are also ridiculous. Commercial TV is suffering as it is from streaming competition and must also adapt, ala' newspapers, to stay relevant in the future.
Finally, using the sport as some political gamesmanship discredits it to those that cannot understand the kneeling controversy. The ignorance seems pervasive and generally reflects the increasing division among the general populace.
I predicted a few years ago that I would be surprised if the NFL was even in business in 20 years and nothing has altered that perception on my part. I only hope that I am wrong since I dearly love the sport far and away above any other.