Despite the chilly weather -- 49 degrees with an 18 mph wind blowing out to left field -- matters grew heated after Columbus starter Carlos Carrasco hit Indians second baseman Brian Friday in the back in the third inning and again in the helmet in the following frame.
As Santana led off the bottom of the fourth, Indianapolis starter Kevin Hart threw his first pitch behind the native of the Dominican Republic and immediately was tossed by plate umpire David Rackley. Unperturbed, the switch-hitter sent the second pitch from reliever Jeremy Powell over the scoreboard in right-center field.
"It was fine, just baseball," said Santana, MLB.com's No. 11 prospect.
After singling in the fifth, Santana led off the seventh with another homer to left, then delivered a two-run double in the Clippers' eight-run frame.
Apart from reveling in the Opening Day victory, Santana was celebrating his 24th birthday -- and it wasn't his first birthday blast. Playing for Double-A Akron last April 8, he went 2-for-4 with a homer and four RBIs.
"I feel good. I'm very happy," he said.
Other Clippers also celebrated with offensive outbursts. Reigning International League MVP Shelley Duncan singled twice and drove in three runs in his return to Columbus, while rehabbing Major Leaguer Russell Branyan went 3-for-3 with a double and an RBI.
Carrasco (1-1) recorded the win, yielding three runs on eight hits over 5 2/3 innings. He walked one and struck out eight.
Alvarez delivered a two-run shot in the third for the Indians and Steve Pearce went 3-for-4 with a pair of doubles. Powell (0-1) surrendered five runs on six hits, including a pair of homers, in one inning.