The National Football League’s first Wednesday game in more than 60 years highlights — and opens — the 2012 schedule, which was released Tuesday, April 17.

As has become custom over the last several years, the reigning Super Bowl champion will play in the primetime season opener — the New York Giants will host the rival Dallas Cowboys on Wednesday, September 5. The opener is usually the Thursday after Labor Day, but with the Democratic National Convention scheduled to conclude that night, and President Barack Obama sure to speak, so the NFL moved the game to Wednesday. It will be the NFL’s first Wednesday game since September 22, 1948, when the Los Angeles Rams beat the Detroit Lions, 44-7.

As usual, the league’s best and/or most popular teams dominate the primetime schedule. The New York Giants, San Francisco 49ers, New England Patriots, and Baltimore Ravens — the four teams that advanced to the conference finals last season &mdash: make a combined 16 appearances on the Sunday, Monday, and Thursday night schedules. Any Sunday night games scheduled from weeks 11 through 17 are subject to change thanks to the NFL’s “flex scheduling” rules, which allow it to shift a more attractive matchup to the 8 p.m. slot.

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While the Giants and Cowboys kick off the week one schedule, the highlight of the opening weekend may be Peyton Manning’s debut for the Denver Broncos. Manning and the Broncos will host the Pittsburgh Steelers in primetime on Sunday, September 9.

Reflecting the renewed interest in the Broncos following Manning’s acquisition, the Broncos will also be in primetime eight days later when they visit the Atlanta Falcons. Overall, the Broncos are scheduled to play five night games as they host the San Diego Chargers Monday, October 1, the New Orleans Saints on Sunday, October 28, and visit the Oakland Raiders on Thursday, December 6.

Six teams — the New York Giants, Denver Broncos, San Francisco 49ers, Chicago Bears, Green Bay Packers, and Philadelphia Eagles — are scheduled to make the maximum five primetime appearances. The Dallas Cowboys, Pittsburgh Steelers, New England Patriots, Baltimore Ravens, Detroit Lions, Atlanta Falcons, San Diego Chargers, New Orleans Saints, Houston Texans, and New York Jets are all scheduled to make four primetime appearances.

Here is a look at some other “hot ticket” games on the 2012 schedule:

Week One: The Packers host the 49ers on Sunday, September 9. The Packers and 49ers were the top two seeds in the NFC playoffs last year and were expected to renew a rivalry that peaked with five postseason games from 1995 through 2001, but the Packers were upset by the Giants in the conference semifinals.

Week Two: The Packers will host the Bears in a renewal of the league’s longest rivalry on Thursday, September 13. The Bears lead the all-time series 92-86-6.

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Week Three: The Patriots and Ravens, who played a classic AFC Championship Game in January, meet in Maryland on Sunday, September 23. The Patriots hung on to edge the Ravens, 23-20, when Ravens wide receiver Lee Evans dropped a potential game-winning touchdown and kicker Billy Cundiff missed a 32-yard field goal in the final minute.

Week Four: The Ravens waste little time getting back on the field as they host the Cleveland Browns Thursday, September 27. The previous incarnation of the Browns moved to Baltimore and became the Ravens following the 1995 season.

Week Five: The Patriots host the Broncos on Sunday, October 7 in a rematch of an AFC semifinal won by the Patriots, 45-10. Of course, the Broncos’ quarterback in that game was Tim Tebow.

Week Six: The resurgent Lions make one of four prime-time appearances when they visit the Bears on Monday, October 22. Last season marked the Lions’ first playoff appearance since 1999 and their first appearances in prime-time since 2001.

Week Nine: Two of the most decorated NFL franchises will meet when the Giants host the Steelers on Sunday, November 4. The two teams have combined to win 10 Super Bowls. The Steelers and Giants played annually in every non-war season from 1933 through 1969 before the NFL merged with the AFL.

Week Eleven: The Steelers host the Ravens on Sunday, November 18. The Steelers (five) and Ravens (three) have combined to win eight of the 10 division championships since the AFC North was formed in 2002.

Week Twelve: Another bitter rivalry takes center stage on Thanksgiving night, Thursday, November 22, when the Jets host the Patriots. The seeds for the modern bad blood were planted back in 1996, when Bill Parcells left the Patriots to coach the Jets. A year later, Patriots running back Curtis Martin signed with the Jets, and in 2000, Bill Belichick resigned as Jets head coach after just one day and eventually landed with the Patriots, who have won three Super Bowls and appeared in two others under his watch.

Week Thirteen: The Washington Redskins host the Giants on Monday, December 3. While the rivalry has faded since the Redskins and Giants combined to win five Super Bowls in a 10-season span from 1982 through 1991, the Giants will be eager to even the score after the Redskins swept the series last year and nearly cost the eventual Super Bowl champions a playoff spot.

Week Fifteen: The Patriots host the 49ers in primetime on Sunday, December 15 in what was almost a rematch of February’s Super Bowl. Both teams were favored to win their respective conference championship games but the 49ers fell to the Giants in overtime.