The new NFL season kicks off on Thursday, with Super Bowl champions New England hosting Indianapolis.
The bulk of the week one action takes place on Sunday, with last year's Super Bowl losers Carolina welcoming Green Bay on Monday.
New England and Philadelphia are tipped to reach this season's finale in Jacksonville on 6 February, but NFL fans have come to expect the unexpected in recent seasons.
The salary-cap era has seen at least one team every year seemingly come from nowhere to reach the NFL showpiece.
In 2004, it was the Panthers, who had a regular season record of 1-15 in 2001, went 7-9 in 2002, then surged to the Super Bowl earlier this year.
They were eventually edged 32-29 by the Patriots, falling to an Adam Vinatieri field goal with four seconds left - his second title-winning kick in three years.
"This game is about 'What are you about this year' because there are new
challenges, new expectations," says New England quarterback Tom Brady.
He should know after beginning his NFL career as a sixth-round draft choice and going on to become a two-time Super Bowl MVP.
Brady admits: "For us to accomplish our goals we are going to have to play better than we did last year."
Philadelphia have suffered partly because of their own fans' high expectations in recent seasons, losing three straight NFC title games.
But the signing of Terrell Owens and Jevon Kearse - the NFL's top receiver and pass rusher - will have done nothing to reign in those hopes.
The Eagles may, however, be hamstrung by injuries, having lost defensive end
ND Kalu and running back Correll Buckhalter for the season, with a dozen more players struggling.
Pre-season injuries have dominated the headlines in recent weeks, with key personnel on several teams dropping like flies.
Washington lost right tackle Jon Jansen with a torn Achilles' tendon in their
first warm-up game on the summer.
Also out for the season are, among others, Tennessee linebacker Peter
Sirmon, Pittsburgh guard Kendall Simmons, St Louis offensive tackle Kyle Turley and Miami wide receiver David Boston.
A knee injury will keep Arizona wide receiver Anquan Boldin, last season's record-setting offensive rookie of the year, out until at least mid-October.
Can rookie Manning do a better job than Warner?
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And two young Pro Bowlers, Chicago linebacker Brian Urlacher and Giants tight end Jeremy Shockey, will start their opening games without having played a down in pre-season because of injuries.
Young players hoping to make an immediate impact in their rookie seasons include number one draft pick Eli Manning - the latest product of the Manning quarterback dynasty - with the Giants.
He is, however, contesting the starting job with veteran star Kurt Warner, a Super Bowl winner and MVP with St Louis.
Another QB, Carson Palmer, last year's top draft pick, looks set to start for Cincinnati after not seeing a single snap in 2003-04 behind Jon Kitna.
Other potential impact rookies include Washington safety Sean Taylor, Cleveland tight end Kellen Winslow Jr, wide receivers Larry Fitzgerald (Arizona), Roy Williams (Detroit), Reggie Williams (Jacksonville) and Lee Evans
(Buffalo).
Running backs Kevin Jones (Detroit) and Tatum Bell (Denver), linebackers DJ Williams (Denver) and Jason Babin (Houston), and cornerbacks Dunta Robinson (Houston) and Chris Gamble (Carolina) are also players to watch out for.
On the coaching front, there are seven new men in NFL hotseats, although four of them are returnees, including Joe Gibbs (Redskins 1981-92) who is back with Washington.