Single post layout based on featured image size

The problem there is that the WP uploader will automatically resize any image you upload to all your specified image sizes, providing the original is larger than the specified size.

Relying on uploading an image between two specific sizes is a very flimsy mechanism for dictating layout. What is actually different about the content of these posts – can they be categorized differently? Can you add a custom field that you can test for in your template and use that to control the layout?