My observations using CSS File Folders so far:
a) mysource_files will not be parsed in a normal CSS file even if it is placed within a CSS file folder.
b ) CSS Design files alone have a performance hit, but within a CSS File folder that hit is removed (served as static file rather than having to come back to Matrix cache each time). The file will serve as 304 on subsequent hits - best performance possible.
c) CSS File Folder *does* seem to have some issues determining which URL to use when you are using mysource_files. E.g. when CSS design file used alone, it matches URL as close as possible to current URL. When placed within a CSS file folder it seems to just pick the first URL. This is only an issue if you are re-using files in CSS Design files - e.g. we had this issue with webfonts I was re-nesting over and over rather than creating duplicates.
d) CSS File Folder also seems to have some issues minifying. E.g if I add normalise.css to the CSS File Folder the resultant CSS that is rendered is valid but incorrect, i.e. some of the rules are incorrectly, differently, or malformed. I either have to remove normalise.css (which defeats one of the main performance gains, reducing the number of HTTP requests) or choose no minification option. Also losing one of the performance gains (smaller payload).
e) Whenever you make a change to a CSS you have to manually go back into the CSS File Folder asset, get locks and re-generate it. It's smart enough to tell you one of the files has changed and the file needs recreating, but not smart enough to do it for you. Makes development painstakingly awful. Have looked for a trigger to automate this - no luck.
For reasons above, despite the better potential performance, I still stick to a single CSS Design File with mysource_files. I would also concede if you had a number of CSS files that change very infrequently they could be candidates for CSS File Folder, but quite a bit of care needed. For the main CSS specific to a site I leave it our of CSS File Folder. I think Squiz were on the right track with CSS/JS File Folders, but I don;t think solution is mature enough yet.
My ideal solution (aka personal wishlist) is a CSS File Folder that parses normal CSS and/or CSS Design files including ./?a= syntax (and creates NOTICES in linking screens for linked assets as an added bonus - I MUCH prefer this to mysource_files syntax) and that automatically recreates a static file whenever one of the linked CSS files is updated. While we're talking wishlists, a CSS Design File that allows defining some string constants, e.g HTML colour codes, so I don't have to type them in all the time.
Oh, and please enhance CSS file assets so they make me cups of coffee.