I have seen a couple articles (e.g., here noting that the prosecution presented a new theory on motive this time around:

Prosecutors in the original trial said Knox and Sollecito, along with a man named Rudy Hermann Guede, had killed Kercher during a drug-fueled sex game in which the British student was an unwilling participant.

. . .

In the Florence retrial, prosecutor Alessandro Crini contended that the motive was rooted in arguments between roommates Knox and Kercher about cleanliness and was triggered by a toilet left unflushed by Guede, the only person now in jail for the murder.

The previously alleged motive had seemed implausible to me, but I can make even less sense of the new one. How did the prosecution argue that Guede and Sollecito had any motive to kill Kercher based on a disagreement about cleanliness between roommates Knox and Kercher? (Although the prosecution did not presumably have to prove anything against Guede, who has already been convicted, I would think they would still need to do something to make sense of his part in the murder.) I have not been able to find any accounts explaining more about exactly how the prosecution argued this new motive.

At any rate, even leaving aside the forensic evidence (or lack thereof), I would think that such a fundamental change in the theory of case would militate in favor of reversal on appeal (i.e., it suggests that the prosecution, rather than basing its theory on the evidence, has instead pursued a strategy of presenting any argument that results in the conviction of Knox and Sollecito), but I don't know enough about the Italian justice system to even know if such considerations are properly part of the appeal.