You can have my Excel when you pry it from my cold dead hands.

But seriously, like with any programming language, once you get used to the syntax it becomes intuitive. The advantage I see for using spreadsheets is that they are portable. You can send someone an Excel spreadsheet and they can look at it, play with it a little, and send it back.

R or Mathematica can do the calculations (and are more powerful than spreadsheets), but you lose the portability.

For simple stuff that I don't need to share I often use interactive Ruby from the Terminal too.