[Anthony]

Unless you're dealing with extremely high performance drives that can basically treat the solar system as flat (acceleration > 0.001 Gs, delta-V > 100 km/sec) you're likely to wind up with some fairly messy orbital mechanics problems. For the high-thrust low-delta-V drive options, hohmann transfer orbits can be optimal, but they're also prone to being very slow.

As far as piloting skill, you're pretty much out of luck unless you give your human pilots precognition; a computer is simply better than a human at deep space navigation, and the problems are mostly solvable (for sails, since they're inconsistent, you'll need to solve in a statistical manner, but that won't make much difference). A computer won't necessarily think of the various multi-pass solutions for gravitational assist, but you're looking at much simpler problems.