Ambitious and unprincipled, De Santa knows that he is fighting a war, and he has to win as the rebels have placed a price on his head. He will do anything for the Army and kill anyone that tries to stop him.
De Santa is portrayed as a cruel, abusive, and sadistic man. Regularly, he has personally participated in the slaughter of civilians that support the rebels and has willingly kidnapped women to satisfy the sexual appetite of his commander, Colonel Allende. He is also a vicious sycophant, who is not above sending competitors on suicide missions for personal gain; he even makes a man dig his own grave before shooting him. Despite Allende's abuse or perhaps because of it, De Santa seems to genuinely admire and look up to Allende, seeing him as a savior of the Mexican way of life. He is also portrayed as a homosexual. In several missions, he is seen looking flamboyantly at Quique Montemayor, a waiter, and can be seen with his arms around him later in the game.
De Santa works alongside John Marston after his first visit to Escalera, sending him on various tasks, oftentimes personally helping John do these tasks. John grows to dislike him, seeing how most of the tasks involve burning down innocent people's homes and capturing young women to give to Allende and the other soldiers. John also obviously hates the idea of a dictatorship, seeing how he fought against governmental control. De Santa tries having John killed a few times, sending John on many missions with incompetent soldiers against large armies of rebels.
Eventually, De Santa betrays John by claiming that the Mexican Army has captured Javier Escuella and Bill Williamson, and insists they are being held in the church at Chuparosa. However, upon reaching said church, John is knocked unconscious by a rifle butt to the head. Upon coming to, he is on the ground, his hands tied behind his back. As he is about to be executed, a lone bullet, fired by Abraham Reyes, whizzes through the air and prevents a seemingly imminent death. In the confusion, a large group of rebels attacks, covering John's escape. Rushing over to Reyes, John has the ropes binding his wrists cut, and hurries back to get his weapons. Unfortunately for Marston and the rebels, De Santa escapes, running back to the safety of Escalera.
In the Luisa Fortuna mission, "Captain De Santa's Downfall", Luisa explains that De Santa was sent to oversee a massacre in Sepulcro. She asks Marston to ride out with a group of rebels and finish him once and for all. Sure enough, John (with the help of his rebel friends) quickly dispatches all the Mexican Army soldiers before beating De Santa to a bloody pulp. Under intense interrogation, the brutalized De Santa tells John that Javier Escuella is hiding at Casa Madrugada. In the end, It is the player's choice whether to kill the captain or leave it up to the rebels. If you choose the second option he will be shot by the rebels and left there to rot in a pool of his own blood, despite the fact he has been beaten so severely he already looks like a corpse.
Captain De Santa's information about Casa Madrugada turns out to be a final lie, as only an ambush of Mexican soldiers awaited Marston.
De Santa's grave is to the far left of Sepulcro when the player enters from the side facing Las Hermanas.
During the mission "Mother Superior Blues", the player will be asked to clear out Sepulcro. Once the coffins have been burned and most of the Undead cleared out, De Santa will emerge from his grave. As he rises, he will mumble, "Mexico loves you, Mr. Marston," in an eerily distorted voice. The player must kill or otherwise disable the Captain to complete the cemetery; you can either kill or hogtie him.
The burgundy color of his shoulder patches signify he is some sort of general staff, meaning de Santa is Allende's in command right hand; de Santa is responsible for the administrative, operational and logistical needs of its unit and supports and advises his commander Allende in running.
If the player kills him, he will be counted as a civilian kill.
It is possible that de Santa is bisexual. There are scenes hinting at a relationship between him and Quique Montemayor, a waiter. In another cutscene, he is seen caressing a woman.
His relationship with the waiter is hinted at in the first cutscene with De Santa, where Quique Montemayor gives John and de Santa a look of longing and desire. In the same scene, as Quique goes to serve de Santa, one of de Santa's guards whispers in another guard's ear and they both laugh, possibly alluding to how obvious de Santa's sexuality is. In another scene, when he is bringing women to Allende with Quique, the two leave with arms around each other. Espinoza also says that he flirts with the bar boy.
When you first meet Abraham Reyes, John tells him he is looking for two men, and Reyes replies with, "You have been spending too much time with Captain de Santa." After de Santa's death, Reyes remarks that "a lot of young boys will sleep safe in their beds."
During a mission, Allende calls him a Mariconcito in Spanish, which roughly translates into "queer".
In a conversation with Victor Melendez, Victor comments about de Santa's cowardice, claiming he'll only attack when a man is on his knees. John comments, "He'll do a lot of things when men are on their knees," further alluding to de Santa being bisexual.
He actually has a lazy eye. If you look at his picture below, you can see it. It is not as noticeable as Eli's, however.
His name translates to Vincent of Saints.
If the Undead NightmareDLC is installed, de Santa's grave is present in Sepulcro even before his death, this may be a programming error or a glitch.
In Undead Nightmare his tombstone reads, "Hombre Tierno, Soldado Feroz", roughly translating into "Tender man, fierce soldier".
If the player leaves the rebels to kill de Santa, Victor Melendez will indicate that the rebels prefer (or would have preferred) that John killed de Santa himself.
He has the same last name as Michael De Santa, a protagonist of Grand Theft Auto V, another Rockstar game. However, Michael's surname was given to him when he entered witness protection; his given surname is Townley.