As he'd done in the Monster of Florence case, Mignini developed an elaborate theory of the crime. Kercher, he believed, had been stabbed during a bizarre sex game gone wrong. It was a game, he claimed, played by Knox, her then-boyfriend Raffaele Sollecito and Diya "Patrick" Lumumba, who ran a Perugia bar where Knox worked part time.
Mignini had to release Lumumba because he had an airtight alibi, and he soon abandoned his sex orgy gone wrong theory. Instead, he argued that Knox killed Kercher in a rage because the roommates had fought over Knox's hygiene and her alleged habit of bringing boys home to cottage late at night. At one point, the prosecution added the allegation that Kercher accused Knox of stealing her rent money. By the end of the initial murder case, the prosecution abandoned all of their shifting motives and said Kercher was killed for no reason at all.
But when police analyzed the crime scene, they found no DNA from Knox. Instead, they found DNA from someone else, a local drifter named Rudy Guede who had a criminal history of break-ins in Perguia and Milan.
"Rudy Guede is all over that room. He's on the victim, he's in the victim's body," said DNA expert Greg Hampikian.
Interpol tracked down Guede, who had fled to Germany. But before he was arrested, Perugia police recorded Guede's Skype conversation with a friend in an Internet cafe. At the time, Guede told his friend, Knox and Sollecito weren't there the night of Kercher's murder.
At some point after Guede met with Mignini, he changed his story. Guede began to claim that Knox and Sollecito were involved in the murder and wanted Kercher dead.
Guede was convicted of murder and sentenced to 30 years in prison. He appealed and received a lighter sentence of 16 years.
"The prosecutor is being very kind to Rudy Guede because Rudy Guede did what the prosecutor wanted," said Judy Bachrach, who covered the case for Vanity Fair. "Amanda Knox -- she says, 'I'm innocent.' Raffaele says, 'I'm innocent.' Therefore, the prosecutor is out for revenge. He wants them to rot in prison forever."
Though Knox and Sollecito were convicted, as they sought an appeal, the DNA evidence against them began to unravel.
Experts found that the bra clasp believed to contain Sollecito's DNA was mishandled by a police investigator. A video showed the clasp was picked up from the floor, handed around and then put back on the floor.
"Anybody who watched CSI knows better what to do," Bachrach said.
Experts also found that the kitchen knife said to be the murder weapon contained such a small sample of Knox's DNA that it should never have been introduced into evidence. As for Kercher's DNA that was supposedly found on the knife, testing revealed it was not actually human DNA but a speck of flour and starch that likely came from rye bread.
In his closing arguments this week, Mignini said there were other reasons to convict Knox, including her lack of an airtight alibi, odd behavior -- she and Sollecito were seen kissing outside the crime scene -- and the fact that Knox at one point stated to police that she had a "vision" that Lumumba was at the cottage on the night of the murder. (Knox, who was interrogated without an attorney present, tried to retract her statement in the morning, saying the police had confused her with their extended grilling and tough tactics.)
Mignini is asking for Knox and Sollecito to be given life sentences. Knox was originally sentenced to 26 years in prison while Sollecito received a 25-year term.
"We made our arguments because we believe in them," Mignini told "20/20" this week. "Now we'll see what the jury decides."
Mignini continues to fight his own, personal legal battle. In January, 2010 he was convicted of abuse of power for impromper wiretaps in the Monster of Florence case. Mignini's lawyer said the wiretapping was authorized and is appealing the conviction.