Are we talking about URLs of file paths
Either way I think both can be ok on Linux/Apache but both will probably have a problem if you ported to Windows/IIS (as if you would for PHP...but nevermind)
I would choose not to though...too easy to mistake a folder for a file and extension and usually I can create enough confusion without adding that into the mix!
actually, probably just file paths and not URLs as I intend to mask/alias the directory to the end user
so a link: real-domain.com/sites/domain1.com/files
looks to the end user like: real-domain.com/media/files
I plan to use an .htaccess re-write like this:
RewriteRule ^media/(.*)$ /sites/%{HTTP_HOST}/$1
so actually the browser will never see the period in the file structure (unless at some point I decided to hard-code in the full file path somewhere in the site instead of using the alias)