I’ve been pointed at the GSoC project, but I haven’t explored its finer points, yet. (Looks like that will take a decent chunk of time.) Practically speaking, I tried to use WordPress with stream wrappers, and I immediately found that wp_mkdir_p() and the GD functions imagejpeg(), imagegif() and imagepng() were incompatible.
I’ve submitted a patch to help the WordPress media uploader better support stream wrappers.
Obviously, this is not as holistic an approach as the GSoC project aims to be, but these are the changes I had to make to store media using a registered stream wrapper.