The biggest plus of this setup is that once it's deployed you don't think about it. It just works and you never think about scaling. Oh and it's cheap (seriously it's like peanuts a month as all you pay for is bandwidth at $.10/GB).
The biggest negative is getting SSL. CloudFront supports it but it's expensive ($600/mo see [2]). Compare that to the pennies it costs to host the non-HTTP site on S3. In our case our cloud app is on completely separate domain (SSL-only) and our public site is informational only so the trade off works. The only SSL enabled link on our public site is for our contact GPG key and it's linked directly to the HTTPS S3 URL.