Double amputee Pistorius, once a national icon for reaching the pinnacle of sport, is accused of murdering his law graduate and model girlfriend Reeva Steenkamp at his home in Pretoria on Valentine's Day last year.
If found guilty of premeditated murder, he could face life in prison. A potential lesser charge of culpable homicide could carry a sentence of 15 years.
Since the trial opened in early March, Nel has portrayed Pistorius as a gun-obsessed hothead who shot 29-year-old Steenkamp four times through a locked toilet door where she was taking refuge after a heated argument.
The defence team says Pistorius, nicknamed the 'blade runner' after his hi-tech prosthetics, was a vulnerable and caring boyfriend who killed Steenkamp by accident after mistaking her for an intruder hiding behind the door.
"The court should have no difficulty in rejecting his full version of events, not only as not reasonably possibly true, but in essence as being absolutely devoid of any truth," Nel told the Pretoria court during his closing arguments.
Nel, known as 'The Pitbull' because of his fierce cross-examination style and penchant for the dramatic, said Pistorius was caught up in a "snowball of lies".
Lead defence attorney Barry Roux began his closing response by accusing the state of deliberately avoiding calling witnesses whose evidence would have damaged their case.
Roux will give the bulk of his wrap-up on Friday, which is expected to be the final day of a long-overrun trial.
There is no jury, and so the verdict hinges on whether judge Thokozile Masipa believes Pistorius' version of events. If she rejects his defence, she would only be able to consider the state's case, circumstantial evidence and the balance of probabilities.
Nel spent the morning session trying to pick apart what he says is the contradictory evidence provided by Pistorius, 27, often shaking his head and holding his hands up in disbelief as he read from the athlete's testimony.
During his cross-examination, an emotional Pistorius said he had fired his gun accidentally without knowing what he was doing, straying from his original argument that he had shot knowingly because he thought his life was in danger.
Nel said Pistorius could not credibly assert that he had shot both deliberately and accidentally.
"The accused never said to anyone that got to the scene: 'It was an accident. The shot just went off'. He never said 'I didn't want to shoot'," said Nel.
"He said: 'I thought it was a burglar and I shot her. Sorry, I shot Reeva. I thought she was an intruder'," Nel said, reading from testimony taken by police after the shooting.
Roux's team has said that psychological evidence shows Pistorius has a 'heightened fight response' because of his disability and he would be more likely to confront danger than able-bodied people.
Nel referred to the part of his cross-examination of Pistorius where he analysed pictures of the couple's bedroom, which he said showed that the athlete's account of how he acted in the minutes before Steenkamp's death was impossible.
Pistorius says the police tampered with the evidence and moved items around the room, which Nel said was an "impossible conspiracy".
"The most devastating aspect of the accused's evidence is his inability and failure to contest the veracity of the scene's photographs ... as to the condition of the scene prior to the commencement of any investigation," Nel said.
"Equally devastating is the vagueness of his version and the how and when the police would have tampered with the scene."
Roux said the defence was not arguing that there was a conspiracy but that there was proof that officers disturbed the crime scene, citing a photo submitted as evidence that showed a policeman moving a bedroom plug.
Another pivotal moment in the case was evidence given by witnesses who said they heard a woman scream prior to the sound of a volley of shots, supporting the prosecution's argument that the couple had an argument and Steenkamp feared for her life.
The defence says Pistorius sounds like a woman when he screams in distress and the witnesses did not hear shots after the shouts but the sound of Pistorius breaking down the door with a cricket bat after Steenkamp was already dead.
Pistorius also faces three separate charges, including two counts of discharging firearms in public and possession of illegal ammunition, all of which he denies.
The fathers of both Pistorius and Steenkamp were in court for the first time on Thursday. The runner, dressed in a dark suit and tie, sat impassively through most of the proceedings.
The killing has shattered the image of Pistorius as an embodiment of triumph over adversity for both his Paralympic victories and his success against able-bodied athletes at the 2012 London Olympics.
The athlete broke down frequently during the trial, often sobbing and vomiting into a bucket.
The closing arguments were expected to last two days, after which judge Masipa, who has more than 4,000 pages of evidence to review, will retire to consider her verdict.
Masipa was only the second black woman to be appointed a high court judge and has a reputation for handing down stiff sentences in crimes against women.