Both went to the Pro Bowl last winter and now lead undefeated teams. This Sunday they'll meet in Big Easy, where Manning grew up and Brees now lives. Their teams will clash in the Louisiana Superdome, where Manning has seen countless games as a fan, and where the fans now pull for Brees.
For Manning, the experience will border on surreal. He used to be one of those screaming fans in the dome trying to make it tough on opposing quarterbacks. Now he'll be one of those quarterbacks trying to overcome the crowd noise.
"I know how the fans think and they are going to be loud," Manning said. "They will be rooting for the home team."
Fortunately for Manning, nothing takes a hostile crowd out of the game like the type of punishing, productive running game the Giants have. Just turn, hand off, and move the team methodically down the field, limiting chances for sacks or interceptions, the types of big plays that get a stadium rocking.
In fact, for all the accolades heaped upon the star quarterbacks of the Giants (5-0) and Saints (4-0), this game could be decided more by defense and running.
By now, the Giants' ability to lean on Brandon Jacobs and Ahmad Bradshaw is established. New York averages 160.4 yards on the ground, which ranks fourth in the NFL, with its mix of Jacobs' power and Bradshaw's speed and elusiveness.
"You've got to have your chin strap fastened, your new mouthpiece in, all your cheek pads ready to go. You better have your shoulder pads strapped down tight when you're getting ready to play both of those guys," Saints defensive coordinator Gregg Williams said. "They're both tackle-breakers. They're both very physical runners. They're both good on yards after contact."
A little more of a surprise this season has been the running game of the New Orleans Saints, which ranks second in the NFL, averaging 166.3 yards. This week, the Saints will have a tandem of their own in Mike Bell and Pierre Thomas, one they haven't had together all season.
Bell rushed for 229 yards in the Saints' first two games, but sprained his right knee late in New Orleans' victory at Philadelphia. Thomas, who did not have carry the first two games while he was coming back from a preseason right knee sprain of his own, took center stage in Week 3 at Buffalo and has rushed for 212 yards and three TDs since.
"It's going to be electrifying because we're going to keep pounding and pounding and pounding," Thomas said. "We've also got Reggie (Bush), who can do just about anything out there on the field, so it's going to be crazy."
The Saints' running game is the reason they've been able to remain unbeaten while Brees' production has fallen sharply in the past two games. In Buffalo, Brees' streak of 22 games with 200 or more yards passing was snapped in Buffalo, and Brees passed for under 200 yards again two weeks ago against the New York Jets.
Brees said defenses aren't shutting him down so much as the Saints have exploited their newfound ability to control games by keeping the ball on the ground and using up clock.
"We went in wanting to take care of the football and run the ball efficiently, which is always what we want to do, but maybe more so against those teams," Brees said. "We just knew that maybe managing the game was maybe more important than trying to be super aggressive. ... We're running the ball well, using up clock, so I think when you look at it, maybe the output wasn't what it was in the past, but the fact that you win by 20 points and 14 points, who cares?"
This could be another one of those weeks for the Saints. The Giants' defense, allowing the fewest yards in the NFL, also has been the league's best against the pass, but 15th against the run. Then again, the Giants haven't played many offensive juggernauts in recent wins over Oakland, Kansas City and Tampa Bay. New York hasn't had to deal with receivers like Marques Colston or former Giants tight end Jeremy Shockey.
"It's not our fault how bad the offenses were that we played," Giants linebacker Antonio Pierce said. "Obviously ... it is one of our biggest challenges all year because the Saints have a great quarterback. They have a lot of speed at running back, obviously Shockey at tight end, the receivers. They are loaded, we know that."
New Orleans also is much improved on defense. The unit still gives up yards, but also leads the league in takeaways with 13, thanks in large part to 33-year-old safety Darren Sharper's five interceptions, two of which he has returned for scores.
Incidentally, Sharper has intercepted Manning four times, returning two for touchdowns.
"Yeah, I am keeping him in the Pro Bowl every year it seems like," Manning said. "When the ball is thrown to him, he makes the catches and makes good plays. You have to know where he is on the field."
This game, it seems, has it all: unbeaten teams, each with star quarterbacks, good running games and good defenses. There are the added subplots of Manning playing in his hometown and Shockey playing for the first time against the team that drafted him in 2002.
Saints head coach Sean Payton called the Giants the best team, with the best quarterback, that New Orleans has faced all season. The Giants have made similar comments about the Saints.
"These are the games that are fun to play," Manning said.