best way is to find a theme close to what you need and modify it. The firebug firefox extension will let you target elements and test out different styles which you can then edit in style.css
You can download artiseer, this is alot like word in regards to layout so very easy. you can make themes and press export to wordpress, drupal etc.
you can download the trial version but that leaves a watermark, or im sure if you a bit naughty you can get round that. depends on you though.
Sure, you can use Artiseer, but if you want to create a good Theme, you’ll want to learn how to do it yourself.
I would go with gerbilk’s suggestion, and learn from an existing Theme.
Also, see the Codex entry on Theme Development
Im not good with CSS and code though. Im only good enough too use it a post and other minor situations
