In addition to moving your multi-gigabyte iTunes library to an external drive, a significant amount of Mac storage space can be freed up by moving your photo libraries onto a separate drive.
If you take a lot of pictures with a DSLR camera or your iOS devices and import them in Photos, you'll fairly quickly run out of free space on most Macs.
This tutorial will guide you through the process of moving an entire library of photos to an external drive, preferably to a much larger external hard drive, in a way that won't disrupt your photography workflow.