Santiago homered for the first time since 2003 and drove in three runs to help the Tigers beat the Texas Rangers 10-2.
"I put a pretty good swing on that one," Santiago said of his 380-foot homer down the right-field line. "I wasn't expecting to hit one that far."
Manager Jim Leyland appreciated the homer, but doesn't want his soft-hitting utility infielder thinking about hitting more.
"If he starts hitting the ball in the air, he's going to be in big trouble," Leyland said. "It's OK if you hit them that far, but he's not going to hit many that far."
"We know our offense is capable of doing this, but we have to do it on a consistent basis," Leyland said. "This was a good step, but we've done this before and then gone back into a slump."
The Rangers are 2-10 since April 11.
"We're in a funk," Texas manager Ron Washington said. "First it was our defense, and now it is the pitching. It seems to have come all the way around on us."
Justin Verlander (1-3) struggled early, giving up five hits in the first two innings, but got out of it with only one run allowed. He blanked the Rangers in his last four innings, giving up one more hit, to lower his season ERA to 5.93.
"I had some trouble with my command early, but I expected that, because I've made some adjustments since my last start," he said. "This isn't exactly what I wanted -- I want to be going more than six innings -- but I'll take it."
Vicente Padilla (2-2) allowed seven runs and eight hits in three innings. Seven of the hits went for extra bases, including three home runs.
"I had a couple good innings, and then things went wrong," Padilla said through an interpreter. "I didn't make any pitches. I don't feel bad, because it was just one outing, but I have to work to get better."
Renteria's single made it 5-1, and Santiago increased the margin to six with Detroit's third homer of the inning and his first since Aug. 1, 2003.
"He just lost his focus," Washington said of Padilla, who was removed after the inning. "He's been great for us since spring. This was just a bad night for him."
Josh Hamilton's sacrifice fly made it 7-2 in the seventh, but the Tigers put the game away with three runs in the eighth.
Leyland announced after the game that Carlos Guillen and Cabrera were going to switch positions, effective immediately. Guillen, who moved from shortstop to first base this season, will now go to third, with Cabrera going to first. ... CF Curtis Granderson, playing his last minor league rehab game while recovering from a broken hand, left Tuesday's game with Single-A West Michigan with tightness in his legs. Leyland said that Granderson will report to the Tigers on Wednesday, and undergo an evaluation before any decision is made about his return to the lineup. ... Padilla had never lost to Detroit, going 3-0 with a 2.08 ERA in four starts before Tuesday.