Napoli's seventh homer and an RBI double by Erick Aybar in the sixth inning ended Romero's homecoming in front of several hundred family members and friends from the former Cal State Fullerton star's East Los Angeles home.
Both of Romero's losses this season have come at the expense of complete-game victories by Santana, in Toronto on April 18 and again on the left coast on Tuesday. It was Santana's seventh complete game of his career.
"When they've got the good stuff like that," Napoli said, referring to Santana's complete arsenal, "it's easy -- and so much fun. You can call anything at any time, and he's going to put it where you want it.
"Ervin had it all going tonight. He got strike one and was trying to put hitters away."
As for his own booming bat, which has produced homers in four of his past five games, Napoli chose brevity.
"I feel good, comfortable," he said. "I'm seeing the ball well. Let's leave it at that."
Napoli doesn't like to chirp when he's in the zone. He knows how the game can humble you in a heartbeat.
"The first 50 or 60 at-bats for [Napoli], he was searching for some stuff," Angels manager Mike Scioscia said. "He found it the last two weeks. He's on a tear, like last year."
Ten strikeouts represented a season high for Santana, who is back in 2008 All-Star form with a 2.98 ERA across his past eight starts. He's averaging 6.9 innings per start with 62 strikeouts against only 21 walks in 69 innings.
"I feel strong," Santana said. "I go as hard as I can as long as I can. I had everything working. My slider was good, fastball command was good. Everybody feels comfortable when we've got a lot of runs. You can go faster."
All three runs yielded by Santana (4-3) came on homers. He didn't allow a hit until Jose Bautista powered his 15th homer with one out in the fifth inning.
Aaron Hill's sixth homer, another solo shot, brought the Jays to within three in the sixth, but the Angels responded with the blows by Napoli and Aybar. The Angels added an unearned run in the seventh.
"He kept the ball down tonight in the strike zone," Jays manager Cito Gaston said. "He didn't get the ball up too often unless he wanted to, and that was probably to brush somebody back. He'd throw a get-me-over curveball or breaking ball, and we swung at a lot of bad pitches, too."
Those bad pitches were good ones for Santana, who used the slider breaking out of the strike zone effectively.
"Early runs helped a lot," Scioscia said. "We set the tone with good situational hitting. That club over there, they swing the bat and drive the ball out of the park. Fortunately, they were all solo.
"Ervin was in the zone early and expanded late. He pitched a terrific ballgame."
Santana also had solid support from his center fielder -- and it wasn't Torii Hunter, who was excused to attend son Cameron's high school graduation. A superb catch by Reggie Willits robbed Alex Gonzalez of a hit before Bautista put a fastball out of the park in the fifth.
"I got a good break on it," Willits said. "It feels good to be able to make a contribution, especially with Ervin pitching like that."
Bobby Abreu's RBI double after Aybar's leadoff single gave the Angels a first-inning lead, and they put together a season-high six hits in the second, including RBI singles by Willits and Abreu, an RBI double by Howard Kendrick and a successful squeeze by Aybar.
Maicer Izturis returned to the Angels' lineup at third base, having missed 18 games with right shoulder inflammation, and delivered a single and walk, scoring twice. Brandon Wood (right hip flexor strain) went on the 15-day disabled list.
With eight strikeouts, yielding a season-high seven earned runs on 11 hits in 5 1/3 innings, Romero (4-2) moved into a tie for the American League lead with Boston's Jon Lester with 72 strikeouts -- four more than the Angels' Jered Weaver.
"I felt good," Romero said. "There's nothing you can do. If you look at the game, there were a few hits that fell for them. That's just the way baseball is sometimes. You've got to be able to overcome those and minimize the damage, and I wasn't able to do that tonight."
Josh Roenicke, picking up for Romero, held the Angels to an unearned run in 1 2/3 innings with three strikeouts working in front of his uncle, Angels bench coach Ron Roenicke. This is a baseball family. Gary Roenicke, Josh's dad, banged the baseball for the Orioles during happier times in Baltimore.