App Engine teaches you to do things right from the start. While it's true you may have a horrendously sub optimal design if you don't take care, there are nice profiling tools you can use to optimize the hottest paths.

As it would be with any platform, making the wrong assumptions about your data model will bite you, and do so a lot more painfully if you wait too long to correct them.

But, it has to be said setting up a similarity scalable infrastructure on a IaaS would also cost you a lot, even if you are not counting your own hours as the sysadmin.

Finally, if you succeed and your hosting bill starts to cost a fortune, you might as well roll out your own Typhoonae or Appscale.