Just watched the last two sets.
This was in no way Federer's fault. He played extremely well and may have just gotten down on himself at the very end.
Isner just barely outplayed him. IT WAS AWESOME!
I wouldn't say Fed played extremely well; he played what he probably thought was 'good enough' to beat Isner. And he was wrong, and by the time he realized that he couldn't find a way back in (especially as by that time Isner was more in the zone).
Fed says he doesn't underestimate any opponent, and I believe that he even believes that. But, it's human nature to do so. He didn't think he was going to lose to Isner on clay and he got burned. Guess he forgot about how Nadal struggled with Isner last year at RG, too.