It very nearly happened on Saturday night before a interception and 56-yard return for a touchdown by cornerback James Pitts finally lifted the No. 1-ranked Wildcats to a 22-10 victory.
"The whole game, I thought we had chance (to win)," Penn's veteran coach Al Bagnoli said. "The problem is you can't make a mistake. The margin of error is nil in a game like this."
Bagnoli's 24th-ranked team made several mistakes that came back to haunt them after Brandon Colavita gave them a 7-0 lead with a two-yard touchdown blast in the second quarter.
There was a bad snap over quarterback Billy Ragone's head that led to a safety for Villanova and set the stage for Angelo Babbaro's 32-yard free kick return and one-yard TD burst midway through the period.
But the Quakers (1-1) kept a Villanova offense that was missing playoff MVP Matt Szczur (sprained ankle) at bay.
When Andrew Sampson drilled a 19-yard field goal with just over nine minutes remaining, Penn edged ahead of the defending NCAA Division I national champions 10-9.
The Wildcats (2-1) struck back with quarterback Chris Whitney (10-of-12 passing, 155 yards, 12 carries, 52 yards rushing) floating a 21-yard touchdown pass to Norman White in the corner of the end zone for a 15-10 lead.
But a two-point conversion pass from Whitney to Dorian Wells was ruled narrowly out of bounds to leave Villanova in jeopardy with 4:29 remaining.
When Ragone (11-of-20, 147 yards, one interception) fired the ball to Blake Adams for a 14-yard gain on an acrobatic catch, the Quakers had a first down at the VU 46 and three minutes to pull out a victory.
"It comes down to a play here and there," said Villanova coach Andy Talley. "On a day like this, when you're not playing very good, you need some big plays and Jimmy Pitts made the play of the game."
Pitts cut in front of a receiver in man-to-man coverage, hauled in Ragone's throw and raced down the sidelines for the clinching score.
"The defense did a get job holding them out on the two-point conversion," said Ragone. "All we needed was a touchdown. I made a mistake and it cost us."
Penn had one last possession after an Aaron Bailey 46-yard kickoff return gave the Quakers a scoring opportunity, but the tough Villanova defense held up at its own 25 to stop Penn on downs.
"So many times you come close, you would eventually like to win one of these games," said Bagnoli. "We've got to start scheduling Towson. We are scheduling the wrong CAA team."
For a coach who has had his share of heart-related problems over the years, you've also got to wonder how Talley holds up in these annual barn-burners.
"You have to give Penn a lot of credit," Talley said. "They are a championship football team and they showed it. I would put them as an upper-level team in the CAA."
The physicality of the contest was every bit as challenging as a CAA game. Szczur sprained his left ankle on his second touch of the game, while VU starting linebacker Anthony Johnson went out on Penn's touchdown drive with what was believed to be a sprained left knee.
Penn's top running back Lyle Marsh left early in the second quarter with what Bagnoli described as a "shattered forearm," after running for 40 yards on eight carries.
There were also numerous other injuries during the night that were not to that level.
Villanova, which avoided serious ailments for much of its championship run last season, has been hit hard in 2010, particularly on both lines.
And then you add Szczur to that mix. For those who wondered all during the off-season how the Wildcats might perform without its star, they found out on Saturday.
"I'm concerned," said Talley. "You can't keep having injuries like this and expect it not to catch up with you in the CAA."
Talley said Szczur is likely to miss practice this week as he rehabilitates the injury and his status for next Saturday's game at William & Mary a rematch of last year's national semifinal is questionable.
"I don't know if we can beat William & Mary without Matt," Talley said.
If Villanova needs to rest Szczur next Saturday, the Wildcats can allow him to recuperate until an Oct. 16 encounter at Maine.
The Wildcats have plenty of other playmakers, like Whitney, White, Wells and running back Aaron Ball who will need to step to the forefront.
Penn, meanwhile, looks to be a team capable of defending its Ivy League championship, with Harvard and Brown coming to the friendly confines of Franklin Field and with co-favorite Harvard losing an Ivy contest on Saturday at Brown.
"This bodes well for us as we prepare for the Ivy League season," Bagnoli said. "This was a real good test for us to go on the road and play well against a really good team."
Talley agrees with his longtime time friend and coaching foe.
"When you play a team every year, you realize when you come out and give your best effort, you have a chance to beat them," Talley said of the Quakers. "Al has a championship level team there. It's not like they are in a down year."