There are two parts to setup,namely, where the user wants to start and how to get to that starting point.
You need to think about where you want to start early on and the selected start point should include how the material is mounted,
how your going to touch off to the part, the intial tool move into the material, how the part will be machined, accuracy of setup, etc, etc.
In many cases common sense will dictate.
RICH