I noticed that Profile Builder was popping its configuration screen the first time I went to any multisite as an admin. So I used an author login, clicked Edit on a comment made with that login, and got "You do not have sufficient permissions to access this page". The url read ' http://test3.<mysitesurl.tld>/wp-admin/users.php?page=ProfileBuilderOptionsAndSettings
This is a pretty serious bug. On a multisite installation, there's a very good chance that a) the multisite administrator is the only one that will be doing any configuration, and b) they will not be doing individual configurations of every blog that's created. So this will hold up the whole works for anyone, admin or not, who attempts to use a multisite blog before the main site admin can configure the plugin.
I would suggest that the best way for this (or any) plugin to operate on a multisite installation is to take the settings from the main blog so that the administrator can establish a common UI. To me that's the most common case people will encounter. If there's a situation where the admin wants different settings on the main site and subsites, adding the option to "apply to main site" and "apply to subsites" in the form of tickboxes would be a good answer for that case.
Please let me know when you plan to update this plugin. I'll be happy to provide testing for it.