Santana's line score wasn't horrible.
8 K, 1 BB, 5 hits, 4 Runs. The problem was the 3 home runs he gave up. I found a few quick points on why he gave up the home runs and it could have been worse.
1. His velocity is down about 2 mph from last season. Here are his velocity numbers from 2011, 2012, and the games with Pitchf/x data this season (pitches in parentheses):
2011: 93.7 mph
3/1: 91.9 (31)
3/7: 91.9 (42)
3/13: 92.2 (53)
3/18: 90.9 (80)
3/23: 90.5 (85)
4/3: 90.0 (98)
He is got slower and slower as his work load increased. Also, the balls which were hit for home runs were in the sub-90 mph range (thanks to brooksbaseball.net)
2. He threw the slower fastball right down the middle of the plate for two of the pitches. Major league hitters can easily hit sub-90 mph fastball in the heart of the plate for home runs.
3. It was cold at the game. Cold balls don't travel far. Santana would have allowed more home runs in the heat of summer. The temperature was 43 degrees at game time. For every 10 degree increase in temp a batted ball travels an extra 4 ft. Two warning track outs to Alex Gordon would probably be HRs later in the year.