Python is my biggest blind spot as a programmer. I don't like it, have bounced off of every attempt to use it. Some things would be easier (Google app engine, etc) if I could just get into it. For some reason, it just mismatches with how I think just enough that I don't.
The opposite experience is Ruby, which I find programming in to be so intuitive and just pure fun. I think that language is the most pleasurable in which I have ever written code.