I use W3 Total Cache to upload attachments to Amazon S3 (origin push CDN). When an image is replaced with Enable Media Replace, the new thumbnails are uploaded to S3, but the image itself is not. Files without thumbnails, such as PDFs, are not updated on S3 at all. Since W3 Total Cache filters
update_attached_file, I was able to trigger an upload by patching upload.php - see lines 104-105 and 156-157 of
https://gist.github.com/dbarlett/5950836#file-upload-php. Assuming this has no side effects, would you consider adding it to Enable Media Replace?