At this present time, I'm running one of our sites, www.ieventus.com, on EC2 and migrated much of our photo data from MySQL to SimpleDB.
I seemed fine when accessing lone images but when visiting a gallery page that has over 2000 image records, that mongrel would timeout.
Right now, I'm creating an Amazon SimpleDB Proxy app (or server) that's uses Rack, Thin, and Memcached for caching. My caching system will be modular, so if you wanted to have a disk based caching system, it would be quite easy.
There was an post by Subbu on A RESTful version of Amazon's SimpleDB that heavily influenced the RESTFUL aspect of this project.
I'll keep you guys posted on my progress.