the problem for many is that 'natural' alignment when standing in an upright static posture does not duplicate the leg/ankle/foot alignment when you pressure the pedals and are in your cycling posture. This can be especially true if a rider tends to knockknee or bowleg. And sometimes the 'natural' alignment assumed while pedaling actually causes/exacerbates knee problems. In which case some supportive measures, like an orthotic/internal wedges/cleat cants, might be called for.
A good start is to get the saddle into a reasonable/good/optimum position and then use a cleat location method that starts from a 'natural' alignment under pedaling duress, and go from there...
often trial and error.
how do you know when its 'right'? do your longest, hardest ride - knees feel OK, done...
or never be statisfied - works also...