I used to just be able to bring iTunes.app into the foreground (even with no window open) and hit the space key to pause/play. I've been using this a lot over the years and it's become one of those habits that would be hard to unlearn.
When iTunes 11 came around (and 11.0.1 soon after), this generally still worked, except sometimes, seemingly at random, after playing a bunch of songs, it breaks, doing random things instead of play/pause (mostly rewind, but sometimes different things too). I've narrowed it down to a problem with the keyboard focus - whenever it happens, the keyboard focus seems to have moved to a random button in the UI, mostly the rewind (<<) one. There is no obvious reason for it to do that, no accidental input or anything.
Is there a fix for this misbehaviour or do I need to get used to a new way of pausing iTunes? This keyboard shortcut is still documented in the iTunes help, so I think it's supposed to work (and does, only not all the time).