Fast melee weapons with a small area of effect (e.g. cutter/flourish/snarble barb) can only reach their full potential with auto targeting enabled, since they will otherwise miss too often.
Weapons that have a large area of effect (e.g. avenger/faust/troika/pulsar) handle much better with auto targeting disabled, since careful aiming can allow you to hit multiple enemies at a time.
If a player is equipped with both type of weapons, there is currently no way for him to use both efficiently without extraordinary effort. Having to hold down the shift key to toggle auto targeting is cumbersome for extended fights. Yet the only other option is to spend several seconds going into the game menu to switch auto target on and off, which is clearly unfeasible in the heat of combat.
The best solution here is to allow players to set auto target independently for each of their weapons. Instead of having a single checkbox in the controls menu, have four in its place instead. (i.e. weapon 1 auto target, weapon 2 auto target, etc.)
Couldn't you just have the auto-target button TOGGLE instead of require it be held, then the game can remember the toggle setting per weapon?