The most significant game of the NFL’s opening weekend is not Thursday’s 100th anniversary celebration between Green Bay and Chicago, Sunday’s prime-time clash between Pittsburgh and New England or even heavily hyped Cleveland finally taking the field.

It is what would otherwise be a diehards-only contest: Detroit at Arizona.

Each finished at the bottom in their respective divisions last year and it would surprise no one if they wind up there again in 2019. Understandably, the game will be broadcast almost nowhere other than Arizona and Michigan.

Yet what happens, or what doesn’t, could shape the way the NFL is played in the years to come.

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Last offseason the Cardinals made either one of the boldest or one of the most ridiculous hires in recent history. They named Kliff Kingsbury their coach despite the 40-year-old having no NFL coaching experience and losing his job at Texas Tech for going 35-40, including 19-35 in the Big 12.

Kingsbury has few credentials and little credibility, yet he does have the promise of implementing the Air Raid offense that made him a star player at Tech, revolutionized the college game (including his coaching of Patrick Mahomes) and has increasingly influenced the NFL of late.

If a total embrace of a spread-style offense somehow works, then expect the league to go copycat, right down to starting a 5-foot-10 quarterback as Arizona will in top pick Kyler Murray, who as recently as a year ago was considered too small to play in the league.

And if it doesn’t, then expect the army of Kingsbury and spread-offense critics to howl in delight.

View photos Make no mistake: Plenty of coaches want to see Kliff Kingsbury fail with the Cardinals. That doesn't mean he's going to. (Getty) More

“It’s pretty-boy football,” Oakland Raiders defensive back Lamarcus Joyner told ESPN. “It [doesn’t] allow the defense to play the game physical like the game was meant to be. When you go against an offense like that, you have to introduce that physicality to them because they don’t want to do that.”

Make no mistake, there is no NFL coach that other NFL coaches are hoping loses more than Kingsbury.

As a group, pro coaches are skeptical, if not downright disdainful, of college coaches who make the leap to the NFL (and take one of their precious 32 jobs). And those are generally the ones who won at that level.

A college coach who didn’t?

Among his peers Kingsbury is considered too young (40), too pretty (isn’t he that dude from “The Notebook”?) and too cute (his Forrest Gump-like ability to be around successful football people doesn’t mean he paid his “dues”).

But what if it works? What if the reason he lost at Tech was a failure to recruit defensive talent to Lubbock (never a simple task), which is a moot skill in the NFL?

What if on Sunday, the Cardinals and their undersized QB gash the Lions, who may not be a Super Bowl contender, but are coached by a defensive-minded Bill Belichick disciple in Matt Patricia?

Suddenly this last-place scheduling abomination of a game has the feel of something … important?

“Guys know that it counts on Sunday,” Kingsbury said. “The sense of urgency has definitely picked up.”

The thing with Kingsbury is he isn’t exactly what his haters want him to be.

Yes, he has the looks and the personality and all of that. He is also the son of a coach from a small town in Central Texas, and a moderately recruited player who embraced the novelty of the Air Raid at Tech under revolutionary coaches Spike Dykes and Mike Leach, and finished with a slew of then-NCAA records.

He was a sixth-round pick who hung around three seasons with five teams. Despite just attempting two passes (only one was completed) he can count as coaches or teammates Belichick, Tom Brady, Romeo Crennel, Josh McDaniels, Jim Haslett, Mike McCarthy, Herm Edwards and Doug Marrone, among others. He’s famously friends with Sean McVay.

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