One day after embattled manager Willie Randolph kept his job - for now - following a much-publicized meeting with ownership, New York improved to 24-26 with its fifth victory in 15 tries.
Helped by some fine defense, Santana (6-3) worked around eight hits and two walks. He allowed three runs and struck out seven, retiring surging slugger Dan Uggla in three key situations.
Duaner Sanchez pitched a scoreless eighth after yielding a leadoff double. Billy Wagner fanned two in a 1-2-3 ninth for his 10th save in 12 chances.
Florida starter Andrew Miller (4-4) lasted only 4 2-3 innings. He gave up four runs and six hits after tossing seven shutout innings with nine strikeouts to beat Arizona in his previous outing.
Cody Ross homered and drove in two runs for the NL East-leading Marlins (30-21), who lost for the fourth time in 11 games.
Randolph stacked his lineup with all right-handed hitters besides Santana, and New York got on the board in the first inning against Miller, a 6-foot-6 lefty.
Jose Reyes led off with a double and moved to third on Luis Castillo's sacrifice bunt. Miller double-clutched on a throw to third that Jorge Cantu couldn't handle, leaving runners at the corners with none out.
David Wright walked to load the bases before Carlos Beltran popped out and Damion Easley hit a sacrifice fly. Tatis, playing right field in place of injured Ryan Church, added an RBI single and Castro made it 3-0 with a single to right.
Ross drove in a second-inning run with a bases-loaded groundout. Wright doubled in the fifth and scored on Tatis' single, making it 4-1.
Ross hit a solo shot in the sixth, the 12th home run Santana has given up in 11 starts this season. The two-time Cy Young Award threw consecutive wild pitches in the seventh, and Jeremy Hermida scored when Reyes bobbled Cantu's RBI grounder to shortstop for his third error in three games.
Castro's RBI single off Joe Nelson in the bottom half pushed the margin to 5-3.
