For the record, I have not personally tried out this product yet but it might come handy someday when I need to generate a template for Drupal or Joomla. I have been working mainly with Blogger and Google Sites (and sometimes WordPress), and their system for developing your own layouts are quite straightforward (and if you're in a bind, there's always the Forums!). Plus, there are tons of free templates in the net.
There's a video on the homepage of the Artisteer website that shows you how easy it is to generate the layout you want then customize it further. First, you will need to choose a generalized layout, then tweak it from there. Sounds very similar in procedure with Blogger's Template Designer.
You will need to cough up some cash to use this product: US$49.96/year for Home / Academic Edition, and US$129.95 for Standard Edition. The main difference between the two is for the latter, it gives you the options to export the template to more Content Management Systems and applications (the Home / Academic Edition is for Wordpress, Blogger, or as XHTML/CSS only).
Maybe I can use this when I'm heavily into website development. But even if this looks like a convenient way to develop websites, I still recommend knowing HTML and CSS, as these really come in handy when the code generated by such systems are not exactly what you had in mind. You can then wade through the code and fix it up!