Plot
Two years after the events of the first game, Jackie Estacado (voiced by Brian Bloom) has become head of the Franchetti family and has learned to suppress the Darkness (voiced by Mike Patton) with the help of a mentally-unstable occultist, Johnny Powell (voiced by David Hoffman). Despite having moved on from his past as a mob enforcer and having established himself as a prominent criminal kingpin, Jackie is still haunted by the memory of his murdered girlfriend, Jenny Romano (voiced by Stephanie Frame), to the extent of seeing lifelike apparitions of her.
While relaxing at a restaurant, Jackie and his crew are attacked by a rival gang. Managing to escape from the gunfire, Jackie sees a stranger with a cane who mentions his late father. Grievously wounded and about to be executed, Jackie is forced to let the Darkness out once more. His powers restored and reunited with his Darkling (voiced by Peter Newman) - a goblin-like familiar of the Darkness - Jackie peruses his attackers into the subway. Amidst the violence, Jackie is mesmerized by a vision of Jenny on the tracks, only to be apparently hit by a train.
His vision blurs and he wakes up in what appears to be a psychiatric ward occupied by his own crewman, including Johnny Powell, who insists that Jackie finds him. Reawakening back into the living world, Jackie regroups with his men at his penthouse estate to plan a counterattack. One of Jackie's closest associates, Jimmy the Grape (voiced by Frank Ashmore), provides a lead that points to Swifty - a smaller crime boss - as being potentially involved in the attack. Chasing Swifty to a construction site, the rogue boss attacks him with a wrecking ball crane.
Finally catching Swifty, he explains that a shady group he met at the Brimstone Club brothel paid him to put the hit on Jackie. Before he can reveal anything else, the Darkness brutally murders him. Before leaving, Jackie collects a cash envelope from his corpse with a seal on it. Returning to his penthouse, Jackie reunites with Johnny, who had left due to the Darkness' influence. Jackie gives him the envelope and orders him to find out who paid Swifty. Vinnie (voiced by Rick Pasqualone) - one of Jackie's men - enlists his contact at Brimstone to help them.
Arriving at the club, Jackie meets Vinnie's contact, Venus (voiced by Anastasia Baranova). She explains that the bordello is under a much stricter management - having closed off the top two floors and with one of her coworkers having disappeared up there - and provides him a gun. Making his way through the building, Jackie encounters armed cultists who know how to use light to disable the Darkness' powers. Caught in a blinding ambush, Jackie is knocked out. Waking up, he finds himself crucified, Venus dead, and a device draining his dark power out of him.
He's greeted by Victor (voiced by William Salyers), the man from the restaurant, who offers to take the Darkness from him in exchange for the lives of his family. Bitterly refusing, he loses consciousness momentarily to find himself in Hell where the Darkness keeps Jenny's soul. After breaking free, Victor is forced to flee - promising to murder Jackie's Aunt Sarah (voiced by Bridger Fox). As the club burns, the Darkness offers Jenny's soul in exchange for the device, the Siphon. Jackie regroups with Butcher Joyce (voiced by Phil Idrissi) and races home.
Johnny explains that Jackie is being pursued by a secret society called the Brotherhood who seek the Darkness' powers for themselves using the Siphon, an object created to contain the Darkness by an entity known as the Angelus, which is the Darkness' female counterpart. After discovering who set up the attack at the restaurant, Johnny then provides a lead to the Brotherhood's location at a nearby brothel. Jackie gains entry through help of a prostitute named Venus and finds that the Brotherhood has been tracking him, his gang, and his family for years. He is then captured by their leader, Victor Valente. Victor orders Jackie crucified, and demands Jackie release the Darkness to him, revealing they have taken over his home. Jackie refuses and falls unconscious from blood loss, he then has a near-death experience in which he argues with the Darkness over giving the entity over to the Brotherhood. The Darkness reveals that it is holding Jenny's soul hostage in Hell, forcing Jackie into fighting back against the Brotherhood. Jackie escapes and races home, mounting an attack with his men against the Brotherhood. Upon reaching his bedroom, Jackie is shot by Bragg, a man who works for the Brotherhood, who then proceeds to murder Jackie's Aunt Sarah. After getting shot in the head, Jackie then experiences another psychiatric ward hallucination, where Jenny and members of his mob appear as doctors, nurses, and fellow patients, telling him that his mob stories are simply hallucinations inspired by mafia fiction. Jackie wakes back in the library of his home with Johnny explaining that he had been unconscious for four days, and that the Franchetti enforcers drove the Brotherhood off before they could make off with Jackie's body.