With two runners on, Granderson crushed Andrew Cashner's 2-2 pitch to right field for his 16th home run of the season and give the Mets a 4-0 lead.
Granderson went 2 for 4, his third multi-hit game since Sunday, and is 6 for 15 with two home runs and five RBIs in his last four games.
Defensively, he made two impressive catches in the eighth: a leaping one by the wall in foul territory down the line, and a diving one in right.
Granderson, after the game, didn't take pride in his individual feats.
"Regardless of what you do individually, there's still the team side of it,'' he said. "We unfortunately were on the wrong side of the coin at the end of the game. San Diego took advantage of all 27 outs.''
Compared to his first-half clip of .243/.340/.417, Granderson's second-half numbers are significantly better at .327/.417/.577, but more revealing of his numbers is his strikeout-to-walk ratio.
He struck out 86 times and walked 45 times in the first half, but over the past 13 games, he has walked eight times and struck out nine.