Prosecutor Alessandro Crini called for 26-year sentences for Knox and Raffaele Sollecito, her co-defendant and former boyfriend, following more than 10 hours of closing arguments over two days. He also said Knox should get four additional years for slander.
Knox and Sollecito deny any involvement in the killing.
Crini departed from past scenarios by suggesting the crime was not so much sexually fueled - an erotic game that got out of control, as the lower court prosecutor described it - but an act of physical violence with a sexual expression.
He alleged that Knox and Sollecito acted in concert with another man in an explosion of violence sparked by tension between Knox and British student Meredith Kercher.
Crini argued that Rudy Guede - a native of Ivory Coast now serving a 16-year sentence for the murder - may have inflamed tensions between Knox and Kercher after he defecated in a toilet inside the the women's apartment and didn't flush.
Crini said Guede, who was friendly with young men living in a neighboring apartment, had done the same thing the previous week. "It is an absolutely disgusting and incongruous habit that he evidently had," Crini said.
Testimony in previous trials had cited tensions between Kercher and Knox over the cleanliness of the house they shared with two Italian roommates.
Kercher's murder in the idyllic hillside town of Perugia is getting its third trial after Italy's highest court annulled an appellate ruling overturning the 2009 guilty verdicts against Knox and Sollecito. They were convicted in the first trial, and sentenced to 26 years and 25 years, respectively. Knox's sentence included 1 year for slander.
Knox's lawyer, Carlo Dalla Vedova, said the shift in the prosecution's theory about events leading up to the killing "confirms the lack of proof."
"In a trial based on clues, all the facts can be interpreted. This prosecutor worked very hard, but it doesn't change the situation. There are too many doubts. It calls for only an acquittal," Dalla Vedova said.
Kercher's body was found in a pool of blood in her locked bedroom on Nov. 2, 2007. Her throat was slit and there were signs of sexual aggression.
Kercher was stripped naked during the attack, and prosecutors allege that her bra was removed with a knife that tore off a clasp, one of the most-disputed pieces of evidence in the case. Guede was convicted in the murder on evidence that included physical evidence from a vaginal swab of the victim.
Crini also urged that Knox's separate sentence for slander for falsely blaming Kercher's murder on a Congolese-born bar owner, Diya "Patrick" Lumumba , be raised from three years to four years because, Crini argued, she lied to deflect suspicion from herself - which would be an aggravating circumstance.
Knox returned to the United States a free woman in 2011 after the appellate court ruling, having spent four years in jail, and has remained there for this trial. Sollecito, who also is free, had attended two hearings but was not in court on Tuesday.
In a statement released in Seattle, Knox said her lawyers had filed an appeal of the slander conviction - the only part of the case confirmed by Italy's highest court - with the European Court of Human Rights in Strasbourg, France, claiming the accusation against Lumumba was coerced by police who failed to inform her she was a suspect in Kercher's murder.
"The police were the ones who first brought forth Patrick's name saying they knew I was going to meet him the night of Meredith Kercher's murder, which was not true," Knox said. "I have stated many times that my original comments about Patrick were coerced by the police and not true."
Lumumba's lawyer, Carlo Pacelli, disputed that in his summing up on Tuesday, saying that Knox named Lumumba "spontaneously."
"Amanda had a double personality," Pacelli said. One the one hand she was "good, compassionate, tender," and on the other "a female Lucifer, diabolical, satanic."
"It is the last one the Amanda of Nov. 1, 2007, at the time of the crime," Pacelli said.
Crini also challenged new interpretations of genetic evidence cited by a Perugia appeals court when it overturned the guilty verdicts. He said a DNA sample on the blade of the presumed murder weapon was clean and belonged to Kercher.
That finding, which was key to the convictions, was cast in doubt during the appeals trial. All of the evidence is up for re-examination after the high-court blasted the appellate court's reasoning.
The trial continues Dec. 16 with closing arguments by the Kercher family lawyer, Francesco Maresca, followed by Knox's defense team the next day. A verdict could come in January.