Intonation is a subtle, deep and vast field. If you're into this kind of esoteric stuff, I am keen to work with players on varying intonation profiles for interesting reasons. These are some general thoughts on intonation theory, see the bridge section for some explanation of my intonation setup on the standard Naiad guitars, my preferred setup.
My intonation settings are based on theory, practical testing and on a combination of listening and measurement across all parts of the fretboard. The 12th is not the only fret on the board. Some players or builders choose to compensate in relation to other frets higher up the neck, or generally flat so that players can easily compensate on the fly with pressure or bends, or they might have different intonation settings or micro tunings for different keys or styles.
Action height is very important to the intonation of any guitar or fretted instrument, as is building any compensation in relation to string material and gauge. The higher the action or stiffer the string the further the string must be displaced, and therefore the more all the other frets will be slightly out even when the octave is compensated to be perfect. All compensation will be a compromise. Usually however it's within the kind of amounts that Equal Temperament is a compromise, theoretically out of tune with itself and with other temperaments. Despite the fixed and equal fret, nut and often saddle locations on traditional guitars, because of string bending and fretting pressure the guitar is a freely micro-tonal instrument during performance and players play it into tune, or deliberately out of theoretical tune constantly, conciously or not, for many purposes. Some will push a string towards the bridge to flatten it, even on a plain steel string- I was certainly suprised the first time I did this.
My intuition is that there is a beautiful inter-relation of geometry and sound at work here in the equal division of a fretboard and in the straight saddle in combination with minimal action height, minimal stress on the strings and optimal string construction. This is something I given much though to in relation to both guitars, music generally and my artwork, which is also based around the form and concepts of relationships of interval.