Santana, who missed all of last season recovering from shoulder surgery, needed just 96 pitches to get 27 outs. It was four days ago, when Wainwright -- who missed 2011 after having reconstructive elbow surgery -- shut out the Padres.
"You have a team that was very aggressive," Santana said. "It was just a matter of throwing the right pitch and locating it in the right spot."
San Diego manager Bud Black didn't think his team came out too aggressive or that his hitters expanded the strike zone against Santana, who threw 74 strikes and just 22 balls.
At one point, Santana retired 16 consecutive batters.
"You know he's going to throw strikes. He was around the plate," Black said. "My conclusion was if we would have taken a lot of pitches, there would have been a lot of called third strikes. It didn't look like we swung at a lot of balls."
The Mets, however, sensed something different.
"At first he was a little up with his fastball, but we were fortunate that they were coming out aggressive, and I think that played into his strength a little bit," said Mets catcher Mike Nickeas, who had an eighth-inning grand slam that broke the game open.
"[Santana] settled down and was just terrific with his slider, I thought, today. His changeup was much better with his fastball command later in the game."
Chances are the Mets (26-21) didn't need the grand slam by Nickeas with the way Santana pitched -- and after they hit two homers in the first inning, courtesy of former Padre Scott Hairston's three-run home run and Vinny Rottino's first Major League blast.
Santana (2-2) got 10 ground-ball outs and allowed four scattered singles -- by Yonder Alonso in the first inning, Chase Headley in the second, Jesus Guzman in the seventh and Blake Tekotte's infield single in the ninth.
Tekotte entered the game in center field in the sixth inning after Cameron Maybin left the game with a sprained right wrist. Maybin isn't expected to miss more than a few days because of the injury.
"Santana has a history of injuries, but today he looked as how I remembered him," Black said. "... The changeup is there and the fastball command is there. He kept us off balance. We couldn't get any consistent swings going."
The same could have been said about the Mets after the first inning and before they scored five runs in the eighth inning off closer Dale Thayer.
San Diego starter Clayton Richard (2-6), dinged early by Hairston and Rottino, allowed two hits and no runs over the next five innings.
"I was able to make a couple of adjustments, but it's tough when you put your team in a hole like that," Richard said. "I was able to throw strikes early in the count. But I wish it could have gone differently."
So do the Padres (17-31). After scoring a season-high 11 runs in a victory here Thursday, they have one run to show for the last two games, both losses. They are now 1-5 on this 10-game road swing that will see these teams play the series finale on Sunday before San Diego heads to Chicago.
This was the fourth time this season the Padres have been shut out and the 22nd time in 48 games the team has scored two or fewer runs in a game.