I'll be cheering for Cotto - I like him, he's a great fighter, he's humble, and he has the potential to be the future of the division; but Mosley is like no one Cotto has ever faced. Arguably the 2nd best fighter in the division, he'll be the toughest test in Miguel's career by far. With Miguel's at times leaky defense combined with his somewhat suspect chin, and SSM Mosley's speed, accuracy, and experience is all going to add up to a long night for Cotto (or maybe a short one if Mosley gets to him early). My pick is Mosley by TKO.
One thing I don't think Cotto gets enough credit for however is his smarts in the ring. He often looks like a rugged brawler, but in the Zab fight (and others) I think he showed a great deal of smarts in the ring and hopefully that will serve him well against another very intelligent fighter in SSM.