I could probably improve my CTR if I found out, for example, my Ads were showing up on Britney Spears Widgets.
Use their keyword tool to find a bunch of nagative matches.
I usually copy and paste the entire keyword suggestion list into a text editor. Then I replace the '*' with " -'. I delete the ones I don't want as negatives. And then I paste the new list back into the AdWords keyword list.
Also, I put quotes around negative phrases.