The thing that puzzles me here is why Knox was ever prosecuted at all. The prosecution had Guede.

The answer is simple and banal: they didn't get Guede until after they had already decided Knox and Sollecito were guilty. Not prosecuting Knox and Sollecito would have required them not only revise to previous beliefs in which they had become psychologically invested, but also to retract previous public pronouncements -- in short, to admit they had been wrong.

From the inside of their minds, no doubt, Knox and Sollecito just felt so suspicious, in the early days of the case before the physical evidence came in and they were relying on behavior to form hypotheses . It's also likely that they were irrationally angry at Knox because of the false implication of Patrick Lumumba that they coerced out of her, and that this anger and frustration at the failure of their own hypothesis morphed into a sense that Knox was an evil vixen.