Speaking from a customer/user perspective: for things where I'll want to interact with other users/customers of the app and where there will be a publicly visible page (i.e. flickr, twitter) it seems to make more sense to use directories. For things where it's more of an internal use only and not visible without being logged in (basecamp, for instance), subdomains seem right. I think that's partly because of precedent from those widely used services, and partly because subdomains feel more private/secure.