- "It would be a shame to get blood all over my nice new outfit. What do you think, Bat-brain, like it? What am I saying? Of course you do! Who wouldn't?"
- ―Harley To Batman
After the failure of one of Joker's more deadly and recent plans, cultivating in a massive Arkham riot and breakout, Joker became deathly ill following an overdose of Titan, a unique steroid compound that was being developed at the asylum and was pivotal to the Joker's designs. Harley remained at his side during his painful recovery from the effects of Titan in Arkham City, aiding him in what would later become his last and most twisted joke on Batman and Gotham. After the Joker's untimely demise, Quinn took complete control over the remains of his gang in her own quest for vengeance against Batman and all of Gotham in honor of the Joker.
Harley Quinn has taken over many of the duties of leading the Joker's gang due to his illness and is more vicious and deadly than previously because of her anger regarding the Joker's health. Harley even supervised the kidnapping of Nora Fries, wife of Mr. Freeze. Shortly after Batman rescues Catwoman from Two-Face, Harley launches an attack on the Arkham City Medical Center and kidnaps one of the doctors, taking her to Joker's Funland in the old Sionis Industries compound, and also implies that the last doctor got executed for failure to find a cure.
When Batman comes for her, Harley is watching over the doctor she kidnapped nearly be executed by Mr. Hammer for failure, until she declares a change of plans and has them execute the medic via the roller coaster. When Batman revealed himself and defeated her gang, she scolds Batman and later disappears into Joker's private office, sealing it behind her, although she also encounters Clayface-Joker and briefly mistakes him for the actual Joker before realizing her mistake, causing Joker to hush her. When Batman arrives, Harley is crying over the dead body of the Joker only to reveal that it was a trap and attacks Batman alongside Joker.
Batman infected with the same poison that is killing Joker, Harley keeps an eye on the Dark Knight as he tries to save Mr. Freeze from Penguin. After his rescue and the creation of a cure, Harley steals it and returns it to the Joker. The Joker, feeling revitalized, starts acting like his old self again and resumes his love hate relationship with Harley. While pursuing Joker to retrieve the cure, Batman finds Harley tied up outside of Joker's office. Batman leaves her and continues after Joker. In actuality, she wasn't able to deliver the cure to the Joker, as Talia al Ghul had intercepted her and stolen it, as well as tying her up outside Joker's office before she could get the chance to deliver it.
Harley was present outside the Monarch Theatre as Batman carried the lifeless body of the Joker out of it and out of Arkham City. She then slapped Batman and dropped to her knees sobbing uncontrollably at the sight. It is implied by guards that she has taken over Joker's operations; nonetheless, her position is tenuous as many believe she would not last without the Joker's support and many members voice desires to defect from the gang or usurp her (some gang members even voice plans to rape her, implying her life is in greater danger then she realizes).
Harley Quinn's RevengeEdit
Immediately following Joker's death, Harley regrouped the clown's gang and staged a trap for officers arriving at Arkham City for payback for Joker's death, but was quickly knocked out by officers and taken into custody. While at a psychiatric ward as Arkham Asylum was being prepared to be reopened, Harley managed to escape and stole explosives from the GCPD, and reunited Joker's gang at the Industrial District in the ruins of Arkham. Ambushing SWAT forces that had been sweeping through the city to find any more thugs to evacuate to Blackgate Prison, Quinn's forces kidnapped two police officers, and kept the district under lockdown from the GCPD, forcing Commissioner Gordon to stage a stakeout on the area. Summoning Batman, Gordon explained about the hostages and Batman enters the district to rescue them, and makes his way to the Steel Mill to find one of two cops. Discovering Harley had a secret base in the shipyard, the Dark Knight interrogates her thugs for information on the base and eventually finds an entrance, as the second cop remains inside.
When the Caped Crusader arrived and rescued two of the officers, Quinn wounded Batman and locked him in an air-tight glass ball in a giant memorial for her beloved. Two days later, Robin arrived and began making his way at the docks and finds Batman's utility belt. Traveling deeper into the docks, Robin eventually comes face-to-face with Batman in the giant Joker shrine, and fights Harley and her henchmen to retrieve her key card to unlocking the ball keeping Batman captive. Returning to the shrine, Quinn unleashes a Titan-enhanced thug on Robin, who defeats it and frees the Caped Crusader. Harley then activates the next step in her plan; rigging the area with GCPD-stolen bombs, forcing Batman to hunt them down while Robin rescues the other police officers.
Realizing she's close to defeat, Quinn calls Batman back to the shrine where her final plan begins- activating the Wonder City mechanical guardians (stolen by the Joker during Protocol Ten) and watching from the ten-foot Joker structure the fight ensuing. Destroying the robots, the Dark Knight then heads for Harley Quinn, who, in her last, final step of revenge activates the bomb hidden in the Joker structure, planning to kill both Batman, Robin and even herself, to reunite her with her beloved.
Batman is able to get Quinn and himself to safety, but soon fears that Robin was caught in the explosion. Harley relishes in Batman's anguish and moves to stab him in the heart to finish her revenge, only to be knocked out cold by one of Robin's projectiles as the young hero reveals himself to be alive and well. Harley Quinn is once again arrested by Gordon while Batman leaves, still scarred from Talia and Joker's death, but Robin assures Gordon that Batman will be fine. With Harley's plans ruined, her gang is rounded up by the Gotham Police and Arkham City is finally, officially shut down for good.