I tend to hop on/off the fence with the whole lock-on targeting thing. You do miss the auto-attack dps benefits, but it's not going to do any good if you're laying dead on the floor or get hit with a debuff from not turning off the lock-on soon enough.

I guess it depends on what you're fighting. If there is a lot of dodging, forget it, it ain't worth it.

But for mostly stationary fights with occasional movement, it's doable to lock on.