Whenever setting people up i like to start from the cleat up to the cockpit.
First thing i do is to set them up neutrally having the 1st metartarsal head line up with the pedal spindle, there is room for fore aft movement for specific applications but to start things off neutral is fine.
The natural gait a human has typically places the toes pointing towards the lateral(out) side a couple of degrees, some 5 some as much as 20(aka duck footed people).
The mistake many people make is to line the cleats up dead straight. Try this on yourself, place the left foot in its natural gait, keeping the forefoot locked in position at the same time bringing the ankle out. Notice what happens with the knee? The Tibia behind the patella will cant towards the centerline of the body or when on the bike it will cant towards the top tube. Just like how the Schleck's ride.
Point is set the cleats up in such a way that allows the footbed to follow its natural gait neutrally without having the heel cups hitting the chainstays.
Once you do that the foot arch wants to collapse. Its a long laborious process to get everything lined up straight, but the end objective is to have all of the following fall on a single plane. 2nd Met, Head of Tibia and the head of the Femur, with regards to saddle height just anything that makes gets your knee angle between 145-155deg. Outside these ranges you would most probably experience pain either on the patella or the posterior region at the head of the tibia.
When viewed from the side almost every human foot's 1st met head will sit higher than the 5th met. This aspect is called forefoot varus. The opposite is called Valgus, a human foot isnt made to walk or move on flat surfaces, thus in cycling or whatever footwear you have its of utmost importance to support the foot as much as you can, i.e. filling up all the gaps. Even before you try to fill up the gaps make sure the arch isnt collapsing and your foot varus/valgus problem is taken care of.
Typically most cycling insoles come with too little arch support, extensive cycling without arch support can lead to Plantar Fasciitis, another area where a lack of support normally exists is the area just below the 3rd met/next to the Plantar Fascia, sometimes people get pain at the base of the metartarsal head as well, one way to go around this problem is to provide your phlanges with some support so as to distribute the load.
There are many custom orthotics out there that can provide enough arch and ankle support but few or none that i know of can offer support at the phlanges. This was what i decided to do and its been working for me, pain at the base of the 1st met head after intense out of the saddle efforts has always been a perennial problem.