Serious injuries can put players out of commission, and teams thought to be contenders in the summer can plummet once the games are actually played.
So let's be foolish. Here's a look at some of the marquee or noteworthy games, as well as games where players or coaches are connected between the two teams.
Kickoff: Dallas at N.Y. Giants
Marquee: San Francisco at Green Bay, Pittsburgh at Denver
- The Packers scored over 40 six times last season; the most Niners allowed in a 2011 regular season game was 27.
- Peyton Manning returns to football, in a new locale.
Noteworthy: Indianapolis at Chicago, Washington at New Orleans
QB's Andrew Luck (Colts) and Robert Griffin III (Redskins), the top two draft picks in April, make their respective debuts with tough road assigments.
Marquee: Detroit at San Francisco
Can we dub this the Backslap Bowl? Coach Jim Harbaugh pissed off Lions counterpart Jim Schwartz last year with handshake bonus after the 49ers won in Detroit.
Connection: Tampa Bay at N.Y. Giants, Washington at St. Louis
- New Bucs coach Greg Schiano earned the job with his work down the road from Giants at Rutgers.
- Redskins gave up a bunch of picks to the Rams to move up and take Griffin III.
Marquee: Houston at Denver, New England at Baltimore
- Manning used to own the Texans while in Indy.
- Pats and Ravens meet in an AFC championship rematch.
Connection: N.Y. Jets at Miami, Green Bay at Seattle
- New York's new offensive coordinator is Tony Sparano, former Dolphins coach.
- Unless rookie Russell Wilson falters badly in first two weeks, Seattle's Matt Flynn will face old team in familiar backup role.
Marquee: New Orleans at Green Bay
What will the over be? 64? Packers won at Lambeau over Saints 42-34 in last year's NFL kickoff.
Connection: Oakland at Denver
Dennis Allen left defensive coordinator position with Broncos to take head coach position with Raiders.
Noteworthy: San Diego at Kansas City
Chargers missed playoffs in 2011 in large part due to the mind-boggling botched snap in KC between centre Nick Hardwick and QB Philip Rivers.
Bye: Indianapolis, Pittsburgh
Marquee: Denver at New England
Peyton Manning and Tom Brady duel yet again, with a twist. Brady holds 8-5 career edge.
Connection: San Diego at New Orleans
Darren Sproles did OK in his first season with the Saints after years in San Diego, amassing an NFL record 2,696 all-purpose yards.
Bye: Dallas, Detroit, Oakland, Tampa Bay
Marquee: N.Y. Giants at San Francisco
Rematch of the NFC title game. Look for poor Kyle Williams not to return any punts.
Connection: St. Louis at Miami
Jeff Fisher said "no thanks" to Miami's offer to coach, choosing to take his talents to East Missouri.
Bye: Carolina, Chicago, Jacksonville, New Orleans
Marquee: Baltimore at Houston
Teams played a tight divisional playoff game earlier this year, and several remain from a thrilling OT contest in 2010.
Bye: Atlanta, Denver, Kansas City, Miami, Philadelphia, San Diego.
Marquee: New Orleans at Denver
Peyton Manning threw a pick-6 last time he faced Saints, in a somewhat important game.
Connection: Indianapolis at Tennessee, Atlanta at Philadelphia
- Luck and Tennessee's Jake Locker meet for first time as pros. Their two Pac-10 meetings were no contest, both going to Luck.
- Mike Vick could face his old team again.
Bye: Baltimore, Buffalo, Cincinnati, Houston
Marquee: Pittsburgh at N.Y. Giants, Philadelphia at New Orleans
Noteworthy: Carolina at Washington
Potential first of what could be several meetings between Griffin III and last year's rookie sensation, Panthers QB Cam Newton.
Bye: New England, N.Y. Jets, St. Louis, San Francisco
Marquee: Houston at Chicago
Connection: San Diego at Tampa Bay, Denver at Carolina
- Bucs receiver Vincent Jackson signed in offseason after seven years with the Chargers.
- Broncos coach John Fox returns to Carolina for first time since being let go by Panthers after nine seasons following 2010 season.
Bye: Arizona, Cleveland, Green Bay, Washington.
Marquee: Baltimore at Pittsburgh, Chicago at San Francisco
Noteworthy: Indianapolis at New England
Andrew Luck, meet Tom Brady.
Bye: Minnesota, N.Y. Giants, Seattle, Tennessee
Marquee: San Francisco at New Orleans
If Alex Smith is still thriving at this juncture, many will point to his game-winning playoff drive vs. the Saints in January as a turning point.
Thanksgiving: Houston at Detroit, Washington at Dallas, New England at N.Y. Jets
Connection: Oakland at Cincinnati
Raiders QB Carson Palmer returns to the place where he spent first seven seasons before leaving on a bitter note.
Marquee: New Orleans at Atlanta, Philadelphia at Dallas
Marquee: New Orleans at N.Y. Giants, Detroit at Green Bay, Houston at New England
The eventual Super Bowl champ Giants were destroyed 49-24 by the Saints last year.
Connection: Kansas City at Cleveland, Miami at San Francisco
- It seems like a quarter of the staff and players on the Chiefs are Browns alum, including coach Romeo Crennel and running back Peyton Hillis.
- Meanwhile, Jim Harbaugh faces the Dolphins for the first time since spurning their interest in early 2011 (hey, it's a theme!).
Marquee: San Francisco at New England, N.Y. Giants at Atlanta
- Tom Brady, meet Patrick Willis. Only time Brady has faced 49ers (in 2004-05), Dennis Erickson was coach and Ken Dorsey QB of the opposition.
- Atlanta's offseason has been fuelled by embarrassing 24-2 playoff loss to Giants.
Connection: Carolina at San Diego
Just think, Norv Turner critics, Chargers could have hired their then-defensive coordinator (and current Carolina coach) Ron Rivera after playoff-less 2008 and 2010 seasons.
Marquee: Atlanta at Detroit, N.Y. Giants at Baltimore
Marquee: Baltimore at Cincinnati, Philadelphia at N.Y. Giants, Kansas City at Denver