eCOMMERCE SITE?

There are literally hundreds of ecommerce options out there. The vast majority of them are hard to theme.

Here are a couple of considerations I suggest (not a complete list, anyone can add, please):

1. What am I selling - this will influence how much money and time you're willing to spend developing the site.
2. Who am I selling to (US only, international etc.) This will influence support for localisation (translation), tax etc.
3. Am I developing the site or someone else? This will be affected by your skill level and how indepth you can do theming. Some carts come with various themes, others have only 1 theme. Some can be themed and some can not.
4. Which technologies are supported by my webhost. These might limit the number of carts that would even work on your host. Unless you're going for a hosted solution. Some hosts already have carts pre-installed.

Personally I go for Drupal with Ubercart. The theming learning curve is hard though. Drupal does have a lot of themes available - just make sure the theme you choose supports ubercart.