Tom, there is undoubtedly a difference, speaking broadly in terms of the use of query strings - at the SEO level - and at the usability / customer retention level.
URLs that are easy to read are easier to remember and easier to copy-paste too - meaning more robust - less likely to break or get corrupted when run through text parsers.
Google is explicit about their preference for clean urls, and a clean url structure for your site as a whole. I'm not sure if this is relevant to where you're at with your particular project, but I always try build a site with a url schema that exposes the information architecture and content priority as much as possible, usually with important pages close to the site root.
If you have to use query strings - and of course they are sometimes unavoidable, or actually just the best tool for the job at hand - Google Webmaster Tools allows you to provide explicit classifications for each parameter. Personally I thought this was a great addition to their suite of tools.