Clint Eastwood, Robert Redford, Rob Wiethoff, and Robert Duvall were all asked to voice the role of John Marston; Wiethoff got the role and the others turned it down.
John Marston drops the F-Bomb less than any other playable protagonist in any mainstream and recent Rockstar game. He only says the word three times in the main story. He also (rarely) says it outside of the story.
The oil drilling Plainview region in the game is a reference to the character Daniel Day-Lewis plays in Il petroliere (2007). In fact, in the area there is a clerk's office with a man sitting outside who looks very much like Day-Lewis' character in the film.
Many references in this game nod to Clint Eastwood's cowboy roles when working with 'Sergio Leone', including a gravestone marked "Cowboy with No Name", an achievement named "More than a fistful" which can be granted to the player who makes more than $10,000 in game and the plot to the Nuevo Paraiso missions, in which the player works for both factions warring over the territory before the factions clash with each other.
John Marston shares many similarities with Red Dead Revolver (2004) protagonist, Red Harlow, including the positioning of his facial scars and the notch in his cowboy hat. Both characters share the facial scar similarity with the lead character from the iconic spaghetti western Il texano dagli occhi di ghiaccio (1976).