Single site vs Sub-sites vs Multi-site installation + Scalability I am beginning a new Drupal project that needs to very scalable and I need to determine what the structure should look like based on the current and eventual project needs.  I have previously used all separate Drupal sites to accomplish similar goals, but would like to at least consider something a little less maintenance-intensive if it makes sense.  Any ideas or advice on how to proceed is much appreciated... thanks.

Players:
-Organization A (main organization)
-Organization B
-Organization C
-Organization D
(and there may be more in the future)

Functions:
-Main public "front area" of site where all organizations land: orga.site.com
-Access-restricted area for members of Organization A: orga.site.com
-Access-restricted area for members of Organization B: orga.site.com/orgb
-Access-restricted area for members of Organization C: orga.site.com/orbc
-Access-restricted area for members of Organization D: orga.site.com/orgd

Access-restricted areas have similar functions between organizations but not exactly the same, and look and feel (theming) would be different for each organization in the restricted areas.

Additionally, each organization's restricted access area would have sub-areas that are further restricted to a smaller group of people, e.g.:

Organization B:
-Main front: orga.site.com
-Restricted area accessible to all members of Org B: orga.site.com/orgb
-Area restricted to a sub-group in Org B: orga.site.com/orgb/groupa
-Area restricted to a different sub-group in Org B: orga.site.com/orgb/groupb

This type of sub-site differentiation would be typical for each different organization.

Normally when I map a project out like this I have a good handle on how to proceed; in this case my head is still spinning a bit, so any input is helpful.
There are many possible ways to build out a site like this.  Right off the top, I would recommend against using a multi-site setup.  c.f. Drush pm-update and multisite.  If you did want to use multiple Drupal sites for this, I would use aliases in your vhost conf file to point /orgb, /orgc etc. to a separate Drupal root.

However, in this particular case I think you would be best off using a single Drupal site with Organic Groups and Organic Groups Theme.  Disclaimer: the latter module is minimally maintained, and I have not used it personally.   If you wanted to support orgb.site.com instead of orga.site.com/orgb, then you could use the Domain Access or Subdomain module instead, although if you use Domain Access you should be aware of the issue Domain Access and Organic Groups.  Try a couple of experiments and see how they fit your use case before diving in and doing the whole implementation; you should be able to set up something pleasing fairly easily.