Well, the are separate entities. The comment field is just a blob of text. The keywords are a list of individual terms. Semantically, think of the first as a description or note and the second as a bunch of tags.
Effectually, there might not be as much of a difference. Both get indexed by Spotlight. App support for the fields is a bit confused and sporadic right now which is unfortunate.
If in doubt, use what makes sense semantically.