The NFL season kicks off on Thursday, when the Carolina Panthers visit defending champions Denver Broncos, who will be led by an unfamiliar face as they begin their quest for back-to-back titles.
Few would have predicted when Peyton Manning ended his career with victory in Super Bowl 50 in February that former seventh-round pick Trevor Siemian would be his replacement, but he will not be the only new face under center in the 2016 season.
Tom Brady's decision to end his Deflategate battle and accept a four-game suspension means Jimmy Garoppolo will get a chance to make a name for himself for the New England Patriots, while rookies Dak Prescott and Carson Wentz have also been thrust into the limelight.
Few stories dominated the headlines as much in the NFL as Deflategate, but the decision of Colin Kaepernick to protest against oppression "of black people and people of colour" by not standing for the United States national anthem has attracted similar attention.
Kaepernick will sit behind starter Blaine Gabbert as the San Francisco 49ers backup quarterback and how Chip Kelly manages that situation in his second chance in the NFL after being unceremoniously dumped by the Philadelphia Eagles is one of several intriguing storylines to watch this season.
The rookie revolution
When Wentz was drafted with the second overall pick by the Philadelphia it was generally accepted he would not see the field in 2016 with Sam Bradford and Chase Daniel ahead of him on the quarterback depth chart.
But Bradford's trade to the Minnesota Vikings in the wake of Teddy Bridgewater's devastating knee injury saw Wentz catapulted ahead of Daniel and into the starting role.
With a hairline rib fracture limiting Wentz to just one preseason game, expectations will be limited as he makes the transition to NFL level, but the same cannot be said of Cowboys quarterback Prescott.
A back injury to Tony Romo has forced Prescott into service, but Cowboys fans could be forgiven for not anticipating a slow start after the Mississippi State product lit up the preseason by scoring seven total touchdowns.
With Prescott supported by fellow rookie and fourth overall pick Ezekiel Elliott at running back, the Cowboys appear in a good position to at least survive until Romo's eventual return.
First overall pick Jared Goff will not be thrown into the fire at quarterback for the Rams on their return to Los Angeles, but the Tennessee Titans' Derrick Henry will be among the other rookies out to make an instant impact.
Old faces, new places
Kelly's appointment in San Francisco was the headliner of the raft of coaching changes that followed the 2015 season.
However, the man known for his up-tempo offense has a challenge to engineer a successful season for a young 49ers team that appears stronger on defense.
Former Cincinnati Bengals offensive coordinator Hue Jackson has been tasked with turning around the fortunes of Robert Griffin III and the Cleveland Browns, while long-time assistants Adam Gase and Doug Pederson have earned their head-coaching shots with the Miami Dolphins and the Eagles respectively.
The Tampa Bay Buccaneers and Tennessee Titans put Dirk Koetter and Mike Mularkey in charge of overseeing the development of second-year quarterbacks Jameis Winston and Marcus Mariota, the latter handed the reins despite an underwhelming interim spell last term.
In New York, the scrutiny will be firmly on Ben McAdoo after taking over as head coach of the Giants following the end of Tom Coughlin's 11-year reign. McAdoo will need to ensure he can maintain the success he had as offensive coordinator and shore up a leaky Giants defense in order to prosper.
If the Broncos are to retain their title then Denver will again need to lean on their defense rather than the arm of Siemian.
Their man challenge in the AFC figures to come from a familiar place, New England, but whether the Patriots are legitimate contenders hinges on if Garoppolo can at least keep them on an even keel while Brady is sidelined and avoid an 0-4 start.
A year-long suspension for receiver Martavis Bryant and running back Le'Veon Bell's three-game ban may hinder the Pittsburgh Steelers' hopes.
The Bengals, whose 2015 season was ended by a playoff meltdown against Pittsburgh, and the Kansas City Chiefs, eliminated by the Patriots last campaign, are well-fancied for postseason tilts.
Carolina's NFC title should come under significant threat, with the Green Bay Packers hoping Aaron Rodgers and slimmed-down tailback Eddie Lacy can inspire them to glory.
Seattle Seahawks quarterback Russell Wilson is considered an MVP candidate as he bids to lead them to a third Super Bowl in four seasons, but Bradford will have to shed his reputation as a first-round bust if the Vikings are to recover from the Bridgewater setback and challenge.
The Arizona Cardinals seem well-positioned to make a deep playoff run again, though their potential appearance at Super Bowl LI in Houston hinges on whether Carson Palmer can shake off his nightmare in last season's NFC title game against the Panthers.