OG mode will create a new top level folder automatically for new groups and will show only Group related folders using a url like {sitename}/filedepot/{groupname}

Drupal offers a variety of solutions to address multiple sites with shared and separate content. As with all things Drupal there is no right solution - just options for your specific needs. Evaluate your goals and make decisions based on them; you may find that Domain Access is a better fit for your content editors or a multi-site setup is much easier to manage for your system administrators.