According to the Codex:
So, it is best to have at least two path segments in your post's permalink structure such as /%year%/%postname%/ or even /posts/%postname%/.
The purpose for this, as most of you know, is because it prevents unnecessary database requests and such. My question is, when it comes to the primary blog on a WPMU install, which adds /blog to all the addresses anyway, would the /blog fulfill this purpose? In other words, can I set my permalinks as /%postname%/ without causing any problems? Since after all this would still result in the address being [domain]/blog/post-name?
Or would it still be preferable to set it to something like /posts/%postname%/? I ask because [domain]/blog/posts/post-name is a little bit less attractive than the former.