I'm not sure what you're trying to minimize. Traffic? Traffic lights? Hills? Through downtown, I don't think you're going to get away from traffic and traffic lights--but I figure that the more traffic the better in those situations because people are more aware. It's the more sparsely populated/faster speed limit roads that seem to be more dangerous in my opinion. Downtown where everyone's slow anyway you're just about as fast as a car, and there's tons of both cars and peds to watch out for if you're in a car.

I don't see how you're going to get out of climbing a hill somewhere. Might as well be Pershing; it's direct at least.

You might want to explore cutting through Balboa Park somehow, if nothing else for a change of pace.

There's a little-updated downtown bike route available online, but I haven't checked it out myself.