Two interesting web sites that I recently came across – one I've tried, one I haven't.
Amplified Journeys from Harmon/Kardon puts together a mix of songs for you based on a road trip that you enter. It finds songs relevant to the places you're coming from, going to and traveling through. I tried a few simple searches and it met with my satisfaction, but personally, I'd rather put together my own mix and use their list for ideas and suggestions rather than just go with it wholesale just from them. Where's the fun in that?
The second one I haven't tried yet, but seems like a neat idea: I Like B-Sides allows you to upload your entire iTunes file (won't that take foreever if you have a lot of songs) and then it analyzes your collection and finds lesser known songs and artists that it thinks you may like. If anyone gives this a shot, I'd love to hear how it goes.