It depends what your goals are. If you are managing backend storage for a web site, most of the tools mentioned are not sufficient. You need control over metadata (headers) and permissions, plus the ability to handle thousands of files efficiently.
If these are your needs, and you don’t want to write scripts (using boto or s3cmd), the best I’ve found is CloudBerry Explorer. It was mentioned earlier, but appears to be someone from the company promoting it.
Nevertheless, it’s pretty good. The UI is clunky, but that’s what you get for working in Windows. Functionally, it’s superb and exposes almost every single capability of S3.
Cyberduck (Windows and Mac) is a close second. It’s not quite as powerful as CloudBerry Explorer, but does give you full control over metadata.
Transmit (Mac) is an absolute pleasure to use, but very limited in terms of metadata manipulation. You can set headers on upload, and that’s about it. You can’t even view metadata of existing files. I’ve also found it to be slow when dealing with large buckets. The S3 functionality has not been updated in a while and cannot create buckets in newer regions like Oregon and São Paulo (though you can access buckets in those regions).
Forklift (Mac) is not nearly as polished as Transmit but is blazing fast, even with large buckets. Like Transmit, it’s very limited in terms of metadata manipulation and not sufficient to manage S3 as backend web site storage.
With that said, both Transmit and Forklift can have a place in your toolbox for those times you need to make a quick change or upload a few files.