Yes a brachistochrone trajectory would be the best way to use these engines. Scott Manley has a good video on how to set these up, including the math and his "eyeball it" method, which is close to the burn target-flip burn anti target-approach you describe, with a way to measure when to flip. As someone else already said, unless you plan to exclusively use the NSW engines a mod that allows you to burn while warping would be nice, if not mandatory (unless you wanna run your computer for hours or days). BetterTimeWarp is another option to PersistentThrust, this mod allows you to modify the physics/non-physics time warp rate, allowing you to even go to x100 physics time warp (although you would need a very stable ship and a very low twr to prevent a kraken attack with this). As a personal suggestion, I would rescale the kerbol system, look into the RSS pack, or install a planet mod that adds distant planets/other systems to visit, as most of the end game engines of this mod would be great to turn those 6-16 year long missions into something more manageable like a 1-3 year long mission