The National Football League will open its 2012 regular season on Wednesday when the Dallas Cowboys visit the defending Super Bowl-champion New York Giants. The off- and pre- seasons have set up several key story lines for the new season. Here are the 10 burning questions for the 2012 NFL season:

How will the replacement referees affect NFL games?

Replacement Refs

Since locking out the NFL Referees Association (NFLRA) in June, the NFL has used replacement officials. They will be on the field when the Giants and Cowboys open the regular season. NFL owners, coaches and players have been critical, if not dismissive of the fill-in refs. The continued absence of experienced officials could affect the quality of play or determine the outcome of a game that might later make a difference in whether or not a team makes the playoffs.

Can the New York Giants repeat?

Eli Manning

Compared to the New York Jets, who generated publicity with the trade for Tim Tebow, and NFC East foes in Washington Dallas and Philadelphia, who have bolstered their rosters, the Super Bowl champion New York Giants have had a relatively quiet off-season. Most fans believe quarterback Eli Manning will continue his productive run, but for the Giants to repeat, rookie running back David Wilson must team with Ahmad Bradshaw the same way Brandon Jacobs did, and cornerbacks Terrell Thomas and Prince Amukamara have to provide support to the leaky pass defense.

How will the ‘Bountygate’ suspensions affect the New Orleans Saints?

Saints Defense

The New Orleans Saints have been among the best teams in the NFL over the last three years, but the suspensions given to them by the NFL for their pay-for-hits bounty system could move the team lower in the NFL hierarchy. Head coach Sean Payton has been banished for a year, while Saints’ interim head coach Joe Vitt is gone for the first six games for their role in the bounty system. Offensive line coach Aaron Kromer will fill in for the first six regular-season games, but he’ll be without linebacker Jonathan Vilma for the entire season and defensive end Will Smith for four games, pending the players’ appeal of the suspensions. Missing out on their experience and talent could hurt the Saints.

Have the Green Bay Packers improved enough to win the Super Bowl?

Rodgers sacked

After a nearly flawless 15-1 regular season, the Green Bay seemed like a lock to win a second consecutive Super Bowl last season. However, the Packers stumbled in the playoffs against the Giants and Eli Manning’s aerial onslaught. It’s difficult to imagine quarterback Aaron Rodgers having a better year than he did in 2011, but the Green Bay defense was often porous and shoddy in the both the regular season and the 37-20 postseason throttling by New York. If the Packers haven’t made enough improvements, they could slip in the NFC.

Can Peyton Manning regain his form in Denver?

Peyton Manning

The last time Peyton Manning played in a game that meant anything, he watched the New York Jets upset his Indianapolis Colts, 17-16, in the playoffs after the 2010 season. After signing a free agent deal with the Denver Broncos in the off-season, Manning has done all he can to assure his new team and its fans that he has recovered from the numerous neck surgeries that sidelined him for the entire 2011 campaign. Despite his enormous past successes, Manning must prove that he is once again capable of being an elite NFL quarterback if the Broncos are to make it back to the playoffs.

Which rookie quarterback will be better: Andrew Luck or Robert Griffin III?

Andrew Luck and Robert Griffin III

Though Andrew Luck of the Indianapolis Colts and Robert Griffin III of the Washington Redskins don’t play in the same division or conference, the two rookie quarterbacks will be measured against one another as a result of being selected with the first two picks of the 2012 NFL Draft. Luck has the bigger shoes to fill after the Colts opted to let franchise hero Peyton Manning leave after he missed 2011 with a neck injury. Washington hopes Griffin III can improve on the combined 18 touchdowns and 24 interceptions thrown by Rex Grossman and John Beck last year. Both of their teams are eager to see if they chose wisely in the NFL Draft.

Will any other rookie quarterback make an impact?

Rookie QBs

While Andrew Luck of the Indianapolis Colts and Robert Griffin III of the Washington Redskins have been given the most publicity, three other rookie quarterbacks — Ryan Tannehill (Dolphins), Brandon Weeden (Browns) and Russell Wilson (Seahawks) — will all start for their respective teams. Each signal caller will rely heavily on help from his more experienced teammates, but, given the lack of game-breaking players elsewhere in their offenses, Tannehill, Weeden and Wilson may have to improvise and adapt often.

Which player will be this year’s Victor Cruz?

Victor Cruz

New York Giants wide receiver Victor Cruz went from an unknown to All-Pro in 2011, thanks to Eli Manning’s prolific passing and Cruz’s ability to break past defensive backs. His out-of-nowhere production of more than 1,500 receiving yards and nine touchdowns helped the Giants win the Super Bowl. This year, another new name may emerge as a blossoming NFL star. Among the many possible players who could elevate their game in the 2012 season: Rashad Jennings of Jacksonville, BenJarvus Green-Ellis of Cincinnati and Davone Bess of Miami.

Will Tim Tebow unseat Mark Sanchez as the New York Jets’ starting quarterback?

Mark Sanchez and Tim Tebow

Despite improving his QB rating and coming off back-to-back AFC Championship Game appearances the prior two seasons, quarterback Mark Sanchez was inconsistent for the New York Jets in 2011. New York’s much-ballyhooed trade for backup quarterback, and publicity magnet, Tim Tebow has to be distracting, even if head coach Rex Ryan has named Sanchez the starter. With the Jets’ brutal early season schedule including the Pittsburgh, San Francisco and Houston defenses in the first five weeks, Sanchez may already be under pressure.

Can Michael Vick stay healthy?

Michael Vick

Few pundits doubt the skills of Philadelphia Eagles’ quarterback Michael Vick. Combined with running back LeSean McCoy, wide receivers Jeremy Maclin and DeSean Jackson and tight end Brent Celek, Vick leads a great offensive scheme that gives Philadelphia many ways to score quickly. However, after consecutive injuries in two preseason games sidelined Vick, there are significant questions as to whether or not he can stay healthy long enough to help the Eagles get to the post-season. Vick’s health will decide the fate of Philadelphia’s season and could affect head coach Andy Reid’s job status.

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