To work out how good a route is, I open up FL companion and...
Flick through bases I might start a run out of. Take a closer look at anything which is above 6k credits per second (for my transport. That's roughly 22 million credits per hour). See what the base that run would go to would sell, or any nearby bases - dry runs aren't completely out of the question if necessary. Repeat for a few more bases. I give preference to places where pirate activity is low, or where the pirates make things enjoyable - Rheinland has recently become a favourite for me, since I've yet to see '2 million or die'. Anything at all going through California is a big no-no.
Also, keep in mind, like Friday said, the cargo value. Gold, for example, is high-risk stuff. A full hold might cost 2 million credits or more. Sure, it's also high-profit, but I'd advise against loading anything but a container transport or freighter with it.
