@nano, I am running it on 3.3.1 with no issues at all, in network mode. Just use the config.php file option found in the wordpress-s3 folder to set it up transparently.
I beleive local copies of the files will always have to be stored, at least for a little bit of time, to let curl do its work to get things up to S3, which can have a bit of latency sometimes when uploading files.
