Though Pettitte ran into trouble in a 41-pitch fourth inning and Jose Reyes and David Wright each homered in the seventh off Kyle Farnsworth, it was the third inning that may have changed the momentum, when Johnny Damon ran the Yankees out of the frame and was gunned down at home plate.
"Hindsight is 20-20," Yankees manager Joe Girardi said. "It's always the toughest decision that a third-base coach has to make."
That third-base coach, Bobby Meacham, waved Damon around on a Bobby Abreu double to right-center, though Damon had to hold up a few moments to make sure the ball fell in.
That cost Damon precious steps, as Luis Castillo relayed the throw from Ryan Church home to catcher Brian Schneider, who blocked with his left foot and barred Damon from making contact with the plate.
"It made sense in my mind just to go for it," Meacham said. "We've been telling these guys we wanted to be more aggressive. We were already up, and I thought we had a chance to add another, but they made the play."
"You run hard until they stop you," said Damon, who commended the call by home-plate umpire Mike Reilly. "The only thing that I probably could have done was know for a fact the ball is going to drop."
The play was one resounding sour note, as the Yankees fell a season-low three games below .500 at 20-23. Though Pettitte turned in a quality start, throwing 116 pitches and allowing three runs in six innings, he was once again struck by one troublesome frame.
This time, Pettitte allowed the Mets to bat around and score three runs in the fourth, enough to send him to his fourth consecutive loss and further frazzle his nerves. He has also lost four straight at Yankee Stadium, his longest losing streak in the Bronx since 1996.
"I know what I'm supposed to do," Pettitte said. "If I'm pitching six innings, I don't feel like I'm doing my job. Whether I go four innings or six innings, we still lost again. For me, I'm sick of thinking about taking positives here. I just want to win a game and try to help this team win. If I don't do that, I'm not going to be happy."
In the fourth, Carlos Beltran's run-scoring single off Pettitte put the Mets on the board and a walk to Moises Alou loaded the bases with none out, but Pettitte began to work out of it by inducing a popout from the struggling Carlos Delgado and striking out Damion Easley looking.
Schneider worked a seven-pitch walk to force in a second run, and Castillo brought in the Mets' third run with an infield tapper that came to rest about 45 feet up the third-base line, pausing as Pettitte bent over in hopes of seeing it foul. Girardi would later call it "kind of a strange inning."
"It's called baseball," Pettitte said. "Things are going terrible, and they're continuing to go terrible. You've got to battle through it. It's a bad inning, but I felt like I was throwing the ball right where I wanted to. ... It's a mental battle that you try to overcome and don't read too much into it. There's not a whole lot that I have to fix."
"The walks hurt him a little bit, but a lot of them were just well-placed balls," Girardi said. "That's part of the game. You have to find a way to get out of it."
The Mets extended the lead in the seventh with three runs on two homers off Farnsworth, as Reyes hit a slider out to right for a solo homer and Wright clubbed a two-run shot to right-center on a cutter. Beltran tripled and scored off Joba Chamberlain in the ninth.
That was enough support to secure the win for Santana, who drew serious interest from the Yankees as a trade commodity during this past offseason -- perhaps most from co-chairman Hank Steinbrenner, who kept the media updated on trade talks and made no secret of his desire to see Santana on the Yankee Stadium mound.
"I didn't really put too much thought into it," Girardi said before the game. "We talked about it, and the whole process, Minnesota took a long time to sort things out. You'd talk about something and then you wouldn't hear anything for a while. They were looking for what they considered the best deal, and they were going to let it go for a while. It did take a while."
For the Mets, it was worth the wait, as Santana was in the Bronx on Saturday but not wearing pinstripes. Instead, the left-hander won his fourth straight decision and remained undefeated against the Yankees, improving to 4-0 with a 2.98 ERA in nine career games (six starts).
Santana worked efficiently into the eighth, allowing four runs and seven hits in 7 2/3 innings. The Yankees scored the first runs of the Subway Series as Jeter, a perennial Mets killer -- now batting .386 with 12 homers lifetime against the Amazin's -- reached Santana for a two-run homer in the first inning, Jeter's second of the season.
Jason Giambi, good-luck charm or no, added a solo home run leading off the seventh -- the slugger's 185th as a Yankee, tying him Paul O'Neill for 15th place on the franchise's all-time list -- before Bobby Abreu cracked another to center in the eighth off Santana.
"He pitched well -- he pitches well all the time," Jeter said of Santana. "You don't want to face him when you're scuffling offensively. I think some guys are swinging the bats a lot better, and hopefully, we carry it into tomorrow."