When we last saw the Eagles, though, they were giving up 276 yards passing to Kerry Collins, who, while technically in Manning's division, the AFC South, certainly isn't in his league as a passer.
Andy Reid's defense will depend on one cornerback, Dimitri Patterson, making his first career start and rookie safety Nate Allen, who was one of Collins' main victims.
If Manning is smiling at that thought, though, he wasn't letting on when he spoke to reporters on Wednesday.
"Philly's always had an excellent team, had an excellent defense," Manning said. "These guys are well coached . . . a diverse blitz team, smart blitzes."
Manning, the ultimate pocket passer, and Vick, a unique running and throwing threat, present vastly different styles, but both torment defenses with their unpredictability.
Vick may leave the pocket at any moment and create a play no one saw coming.
Manning does his deception before the snap, adjusting his offense on the fly. His line of scrimmage gyrations are by now familiar to fans and to cornerback Asante Samuel, who has faced Manning eight times.
"It's freaking annoying. I freaking hate it. But, you know, that's why it makes him one of the best players ever," said Samuel, a former Patriot familiar with battling the Colts.
Samuel and cornerback Ellis Hobbs, another ex-Patriot, said defenders have to ignore Manning's displays and focus on their own plays. Both said the keys to disrupting the quarterback are playing physical with the Colts' receivers and using a mix of coverages.
"You've got to keep him guessing," said Hobbs, who will likely be sidelined with a hip flexor injury.
Quarterback pressure will also be critical. It might come through blitzes, but, ideally, the Eagles would like to get at Manning with just four men, leaving more defenders to cover the receivers.
"I've yet to meet a quarterback that likes to get hit," Hobbs said. If the Eagles can hit him and confuse him, "he'll become like any other quarterback, disarrayed, and he'll make his mistakes here and there."
Manning has rarely been like other quarterbacks, though. He attributed his consistency to a unique dose of good luck: "I've really only played in three systems in my football career - one in high school, one in college, and one in the NFL."
The Colts got off to a slower than usual start in 2010 and have suffered a rash of injuries on offense, but Manning has kept rolling. With tight end Dallas Clark out for the year and wide receiver Austin Collie and running back Joseph Addai missing Monday's game, Manning turned to a slew of backups.
Five Colts caught three passes or more, including tight end Jacob Tamme, whose six receptions doubled his career total.
"He's like the great point guard that has the ability to make others around him even better," said Colts coach Jim Caldwell.
Manning said the Eagles present a challenge in the way they create turnovers. The Birds' 11 interceptions are fourth best in the NFL.
Manning, though, has thrown just two picks this year, tied for fewest in the league, against 15 touchdowns, second most. In his previous matchups with the Eagles - in 1999, 2002, and 2006 - he threw seven touchdowns and one interception. The Colts won all three times.
Contact staff writer Jonathan Tamari at 215-854-5214 or firstname.lastname@example.org.