In season one, "Sanny" was a detective in the Homicide Unit who was sent with Jimmy McNulty into the Barksdale Detail in order to spy on him for William Rawls. Rawls sent him to the detail because "Sanny" was one of the unit's more inept homicide detectives, with a less than 40% clearance rate whose excuse for his performance is a lack of "dunker" cases (easy cases). He tries to resist, stating that it isn't his job to inform on a fellow cop and Rawls orders him to solve one of his open cases, all of which are "Whodunits" (difficult cases), inform on McNulty or leave the Homicide Unit altogether. Sergeant Landsman recommends a psychic, Madame LaRue, and Santangelo desperately tries her. "Sanny" follows her instructions to bury a doll at the cemetery. That evening, McNulty solves one of the open cases, and Santangelo doesn't understand why a different case got solved. Landsman informs him that Bunk and McNulty did his work for him through a witness Omar Little. With the clearance, Santangelo is able to refuse Rawls's demands and is grateful enough to inform McNulty that Rawls actively wants to fire him.
He is demoted to patrol officer at the end of season one for failing to give Rawls anything else useful. In season two, he is seen briefly as a beat officer, arresting Bubbles and Johnny Weeks when they try to steal medical supplies from an ambulance responding to an overdose. In season three, he drives the narcotics wagon in Major Colvin's Western district - a large prisoner transport vehicle used to round up drug dealers. When he encounters former Barksdale Squad members McNulty and Kima Greggs, Santangelo mentions that he is apparently happy at being a patrolmen as his job is easier. As he is no longer a detective, he no longer deals with commanders such as Rawls and still takes home the same pension thus making him happier. He remains a partrolman in the Western District in season four, when McNulty transfers in alongside him. During a counter-terrorism seminar, he was the first officer to point out the uselessness of Western District officers learning anti-terrorism tactics in a crime ridden district. Santangelo is also one of several officers present for the arrest of Omar Little on a murder warrant.