If you haven't heard of McCain's Spain gaffe, the basic summary is that he was doing an interview with a Spanish news organization and, if you go by the transcript, it seems like he doesn't know who the Spanish Prime Minister is, or even that Spain is in Europe.
Listening to the audio, it's pretty clear that he was either not paying attention, misunderstood the interviewer, or simply couldn't hear her, so he decided to bluff with some boilerplate about our friends and our enemies.
Which is fine, really. I mean, yeah, I'd rather his first instinct wasn't to bluff like a pleb caught napping in class, but whatever. But as Matthew Yglesias points out, he seems to be willing to piss off a long-term ally rather than admit to a mistake.
That's definitely a problem.