I think it's fine to look for a profitable route. If you're looking for THE ONE more profitable route it's quite easy to find too, just follow the myriad of threads about traders bashing pirates bashing traders bashing terrorists and you'll figure it out.
Also, there's the threat aspect of the routes you'd have to put into your count there. How much money will I have to drop from time to time and how much time will I lose trying to shake pirates.
Then again, you could try and look around for the shipping and other private companies. Pick a region in space or two and figure which companies operate in the area. Think about someone that will work on that company and figure him/her a nice story, it doesn't need to be a novel, just a paragraph saying what that character is about, what's he like and stuff like that. Try and find some quirks for him, some personal traits and so on. It would be nice also for you to really associate with that company, go it's ID and tag, instead of the common Trader ID, Police tag.
Then you start worrying about what route is best inside the region you picked. To be honest, that are some three companies that have enough reach that you can travel as far as the border worlds without infringing any RP standards.
EDIT: I just saw the sub title... I shouldn't have posted here, I'm no genius. I'm very sorry.:crazy: