Ghacks.net has a great, in depth article on how to set up a content distribution network in WordPress using Amazon S3. The guide gives you the ingredients needed and walks you through the entire process of installing and configuring the W3 Total Cache plugin, setting it up to use the CDN, getting an S3 account, etc.
It takes between one and six hours to configure and activate a CDN on the WordPress blog. Most of the time is spent waiting for the DNS to propagate, the account to become active and the data to be transferred. Webmasters should check the speed of their website in Google Webmaster Tools (or other tool) to see if the changes have decreased the load time for the users of the site. They should also monitor the costs over at Amazon.
On the flip side, I’m currently using WPCDN on WPTavern.com and it was easy to setup. Even though they have a plugin to use, W3 Total Cache made it even easier to setup thanks to its built in way of handling different types of CDNs. I’ll be using this CDN for a month and then asking you if the site has loaded any faster.