216 diffusion, in my experience, is mainly used to place in front of lights in order to achieve a softer quality of light. It is pretty thick, meaning you cannot discern an image through it. Thats what makes it good as a diffuser, because the light source doesn't shine through. Instead, the light source is "fattened" by it, resulting in a larger effective source and thus softer light.
220 Frost, if I'm remembering the correct one, is also called Opal (if I'm thinking of different frost, someone let me know). This is a thinner gel that you can discern blurry images through. The main use I've had for frost is using it to cover windows. It knocks the light down a little bit and blurs out the background, giving the window a very nice glowing "frosty" look. Also in my experience frost tends to be less effective at diffusing lights that you place it on because the gel doesn't spread the light across its surface as well as 216 does.
Most of the films I work on have a good amount of frost, but an even greater amount of 216.
I hope this helped. I'm sure other people have some good advice as well.
