Assuming you want Windows, try the fast & free application called Duplicati:

http://code.google.com/p/duplicati/

Their 1.0 release is out and works excellently with S3. It can't be set up as a Windows service yet, but that functionality is on its way.

For Linux, my favorite is another free utility called Amanda Network Backup:

http://amanda.org/

Supports S3 and MySQL backups. Really easy to set up and has commercial support if you need it.