First click doesn't register? For some reason, from time to time, I'll have this issue where the first time I click something, nothing will happen. But, the second time I click the exact same spot, it will work as normal. This usually lasts about a day, then it goes away. It can return in a day, or in this case, after a 3-month hiatus. It is extremely annoying having to double-click everything (or tripple-click where a double-click is required). What might be causing this? It seems like the same issue described here, but I don't have jiTouch or BetterTouchTool. It is not resolved with a reboot, or even an SMC reset.

Macbook5,2 (2009)
In this case, it was caused by Spotify. It may have something to do with the ads that refresh every 10 seconds, but it started happening immediately after I opened it a minute ago, the 3-month hiatus ended the day I reinstalled it, and it usually happens in about hour-long increments, about how long I usually have Spotify open. I'm now 100% sure of this, it directly correlates with when the app is open or closed. It's strange, though, the window I'm in doesn't appear to lose focus, and this even happens when clicking on something in Spotify, but Spotify is what's causing it beyond a doubt.