I just used Smush.it to optimise a couple of images on http://lanyrd.com/ (the logo and the background image) and it knocked a good 5KB off the page load - not too bad at all.
Our filenames are generated from the truncated SHA1 hash of the file contents, so logo.png becomes logo.16c7e567.png - which means we can safely set a far-future expires header and serve through Amazon CloudFront without worrying about changes to the images, JavaScript or CSS not propagating to the live site.
Depending on how many images you have. Doesn't that mean that it has to download each image and then re-upload them? Could be quite a cost for minimal savings if you have a large number of images to store.
Edit: I'm talking about 20,000+ product images, not the images or files associated with a layout.
Our filenames are generated from the truncated SHA1 hash of the file contents, so logo.png becomes logo.16c7e567.png - which means we can safely set a far-future expires header and serve through Amazon CloudFront without worrying about changes to the images, JavaScript or CSS not propagating to the live site.