"...And another angel came out from the altar, who had power over fire, and he cried with a loud cry to him who had the sharp sickle, saying, “Thrust in your sharp sickle and gather the clusters of the vine of the earth, for her grapes are fully ripe.” So the angel thrust his sickle into the earth and gathered the vine of the earth, and threw it into the great winepress of the wrath of God. And the winepress was trampled outside the city, and blood came out of the winepress...

I always took it to be a reference to the above eschatological conclusion: that he was drawing a reference to the trampling of humanity at the end of days.

You're not the first to be flummoxed by the idiom. When the book was newly translated into Japanese Steinbeck's wife was talking to a Japanese man at the press opening who told her how wonderful the book was but puzzled by the title. Apparently it had been translated into Japanese as "The Angry Raisins"...