I began using Multisite just a few months ago, and am really loving it. You’re going to want to use the sub-domain structure if you have a host that supports it. I use a Media Temple Grid Server plan. It will allow you to create a subdomain and then mask it with a symbolic link. i.e. rtgibbons.mynetwork.com would be mapped as rtgibbons.com or whatever URL you want presented.
Upon a Google search, I found that as long as you plan to use Domain Mapping, there will be no advantage to either method.
http://wordpress.org/support/topic/multisite-subdomain-vs-sub-directory-setup?replies=4
I’d suggest subscribing to the WordPress.org Multisite Forum. There is very good info over there and Andrea_r is very sharp.
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