So of course, the Indianapolis Colts' defense -- yes, the one that let the Titans come back to win in December -- made the plays that mattered most.
Manning threw for 312 yards and a touchdown, and the Colts held off Tennessee for a 22-20 victory Sunday when their defense stopped Young on a final-drive comeback.
"Our defense saved the day, and that's what good teams do," Colts coach Tony Dungy said. "They find a way to win."
This time, the Titans (1-1) trailed by 13 points instead of 14.
"Anytime the ball's in Vince Young's hands, everyone feels like we're going to win the game," Titans defensive end Kyle Vanden Bosch said. "We were just waiting for something magical to happen."
But unlike last December, when Rob Bironas capped a similar comeback with a 60-yard field goal, the Colts collapsed around Young on fourth-and-4. That forced him to lob the ball away in the final seconds.
Manning kneeled down to run out the clock as defending champion Indianapolis (2-0) reminded Tennessee which team remains atop the AFC South.
"The defense came up big," Manning said.
Vinatieri had one of his worst days in years despite making field goals of 22, 39 and 20 yards.
He had an extra point blocked and a field goal partially blocked that bounced off the crossbar before going over. He also missed a 36-yarder to the left after the Colts recovered a fumble in the fourth quarter.
"There were some things out there I've never seen before," Titans coach Jeff Fisher said. "I've never seen a ball tipped, and then hit the cross bar and go in. That's the good fortune of the world champs."
The Colts had every reason for a letdown in their first road game after unveiling their title banner before the opening 41-10 rout of New Orleans. And they played without starting linebackers Freddy Keiaho (right elbow) and Rob Morris (ribs).
Indianapolis allowed Tennessee 313 yards, including 141 yards rushing. That was well below the 282 yards the Titans had in their opener.
The Colts nearly blew a 16-6 halftime lead. Vinatieri struggled and the Titans picked off Manning and sacked him twice in the second half.
The Colts have had a great run against AFC South foe Tennessee recently, winning eight of their last nine with Sunday's 22-20 victory. Not surprisingly, Peyton Manning has had a big influence in his career vs. the Titans.
Record as Starter
Indianapolis twice had the ball at the Tennessee 8 and had to settle for field goals. They even came up with a fumble when linebacker Tyjuan Hagler, starting in place of Keiaho, recovered at the beginning of the fourth period.
But Tennessee, which gave up more yards than any other NFL defense in 2006, had to settle for two field goals before LenDale White scored his first pro TD in the third.
The Titans held the Colts to a three-and-out after the turnover. But Vinatieri, the kicker signed last year for his accuracy in the clutch, missed a 36-yarder.
"We won, and that's the only thing that's really, really important," Vinatieri said.
Young, who stopped a drive himself with a taunting penalty just before halftime, drove the Titans 74 yards and pulled them within 22-20 with a 2-yard pass to Roydell Williams with 6:02 left.
Manning had his own chance to seal the victory. But Titans cornerback Nick Harper, who won a Super Bowl ring with the Colts in February, leaped up and tipped away a pass intended for Harrison at the goal line. Then Vanden Bosch sacked Manning on third down, forcing the punt.
"We were trying to get a touchdown and put the game out of reach," Manning said. "We didn't do as good a job as we wanted of running the clock."
Young, who looked so poised in becoming the first rookie quarterback to lead two comebacks of 14 points or more in 2006, finally showed his youth.
He stopped a drive just before halftime when flagged for taunting after running out of bounds, and Manning drove the Colts to a field goal after getting the ball back.
The Titans had 98 seconds left and needed a field goal to win and improve to 2-0 for the first time since 1999. Young was sacked on the first play. He overthrew Brandon Jones on third down, then the Colts collapsed around Young on fourth down and he fumbled.
Left guard Jacob Bell grabbed the ball for the Titans, but that was it.
"We fought hard. We played well. We just didn't finish it," Young said.
Vinatieri came into the game having connected on 409 of 416 extra points. He hadn't missed on an extra point since 2005 while with New England when he went 40-of-41 that season. ... Manning passed both Boomer Esiason and Dave Krieg into 11th on the NFL's all-time yardage list. ... Harrison passed Cris Carter for fourth on the career yards receiving list. He came in needing 123 yards to pass James Lofton for third, but Harrison had 87 yards. ... The Colts now have won 36 of their last 43 and haven't lost in September since the 2004 opener. ... This was Fisher's 200th regular season game, and his record now is 106-94.