The answer is it depends.
Gut/Poly is best for me but I want extra power and feel from gut and mains determine approximately 75% of how a rackets feels and plays. Poly cross adds spin potential, keeps the strings from moving around, and add directional control.
If I thought a racket had too much power and/or I played mostly baseline bash tennis, I might go poly mains with a soft cross but I am too cheap to use gut as the soft cross because it is too expensive. Gut is too expensive for a cross when the mains determine 75% of how the racket plays. So, I would use poly mains with a syn gut or multi cross.
If you like to volley and play all court tennis and racket is not too powerful or lively, I would use gut mains with poly cross.