How to Leave Programs on One Drive and Data on Another

Can I have OSX on one drive and data files on another drive such as in internal or external SSD boot drive and User Files on the hard drive. I created this and seemed ot be having different errors accessing software, etc that I out everything back on the internal iMac hard drive until i figure out how it is done successfully. Even if I mount the SSD internally I would think I would have the same problems. Any advice? Thanks, Bill