"I'm pretty comfortable with what I threw," said Hoffman, baseball's all-time saves leader whose second blown save in six chances is sure to set off more debate on talk radio shows and Internet fan forums. "Obviously it wasn't good enough.
"He's a pesky hitter, tough to put away," the 40-year-old Hoffman said. "He went down and got a pretty good pitch, down and in, and was able to hit it out. Sometimes you don't like to tip your cap, but he went down and got a good pitch."
Rookie Emmanuel Burriss doubled leading off the 13th and scored the go-ahead run on Fred Lewis' single.
It was San Diego's first home game since a 2-1 loss in 22 innings to the Colorado Rockies on Thursday night. That means the Padres have scored only three runs in their last 35 innings at Petco Park. San Diego has lost seven of eight and dropped into a tie with the Giants for last place in the NL West.
Molina homered to left on a 1-2 pitch, his fourth.
"You don't see that happen a lot," Giants center fielder Aaron Rowand said. "Hoffman is one of the best; he is the best. He has been for a long time. He's the smartest pitcher I've ever faced. Even the best make a mistake."
That one pitch by Hoffman, whose ERA rose to 8.22, wasted a brilliant effort by Maddux, who was trying for the second start to become the ninth pitcher in big league history to reach 350 wins.
Maddux, 42, was much sharper against the Giants than he was Friday night, when he allowed a career-high nine earned runs in a 9-0 loss at NL West-leading Arizona. Mad Dog allowed four hits -- including three doubles -- in seven innings, struck out five and walked none. He retired 14 batters by groundout.
"A guy went down and hit a good pitch tonight," Maddux said. "Every now and then you've got to tip your hat."
Maddux said Hoffman will be OK.
"Being a closer is the hardest job in baseball, especially after a night like this," Maddux said. "He's been down this road a few times. He'll be OK. I hope he gets a chance to save the game tomorrow."
Burriss, whose contract was purchased from Triple-A Fresno on Sunday, doubled down the right-field line opening the 13th off Glendon Rusch (0-2), who also was the loser in Thursday night's marathon. Lewis singled to short center and Burriss beat Scott Hairston's throw home to give the Giants a 2-1 lead. Rowand singled in Lewis with two outs.
"This is a great opportunity," said Burriss, who entered the game as a pinch-runner in the eighth and stayed in at shortstop. "I felt real energized because I'm young and didn't come in until the eighth inning. Guys get tired in the late innings. You have to take advantage as much as possible."
The Padres loaded the bases with no outs in the bottom of the inning against Brian Wilson before rookie Colt Morton hit a sacrifice fly for his first RBI. Khalil Greene flied out to center and Josh Bard walked to load the bases again. Tadahito Iguchi forced Bard to end the game.
Wilson got his sixth save in seven chances. Keiichi Yabu (2-1) pitched two-thirds of an inning for the win.
After Brian Giles hit an RBI single off Matt Cain with one out in the fifth, four Giants pitchers retired 19 straight batters until Adrian Gonzalez singled to right off Merkin Valdez with two outs in the 11th. Kevin Kouzmanoff followed with a single to right to move Gonzalez to third, but rookie Callix Crabbe flied out to left.
Molina's homer got right-hander Cain off the hook for a loss, although the his winless streak reached 10 starts. He hasn't won since Aug. 28.
The Padres had four straight singles off Cain opening the fifth, although Bard was thrown out trying to stretch his leadoff hit into a double. After Iguchi singled to left with one out, Maddux showed bunt but swung away, slapping a single to left. Giles then singled to right to score Iguchi. Giles had been hitless in his previous 16 at-bats against Cain.
Cain also went seven, allowing one run and five hits. He struck out seven and walked three.
Cain also allowed nine runs in his last start. According to the Elias Sports Bureau, it was the sixth time two starting pitchers matched up after having given up at least nine runs in their previous starts. The only other such matchup in the last 70 years was Andy Benes of St. Louis against Osvaldo Fernandez of Cincinnati on June 4, 2001.