I come from an After Effects background, so the idea of having to prep a dozen different versions of every asset to create banner ads of different sizes is a major speedbump to our workflow. I'll usually run it on the final exported assets folder before uploading to the ad network. TinyPNG seems to reduce the file size even better, but they don't have a desktop application. They do, however, have a plugins for Photoshop and Wordpress. AND a developer API... Hint hint.
While we're at it, am I missing the panel where you can set the master preference for optimizing, preload, etc for all assets in one place? Then setting those flags manually for individual images can override the global setting.