The distance of the adjacent signal layer in PCB stackup
It depends on what the signals are.

In a 6-layer PCB, you've probably got quite a lot of parallel buses to get from place to place.  So common technique is to route each of the two adjacent signal layers with tracks perpendicularly as much as possible; one of the layers predominantly 'north-south', and the other layer predominantly 'east-west', avoiding parallel runs in close proximity as much as possible.

If that isn't significantly possible, and if the signals are significantly likely to cross-talk to others, then physical separation (in the X/Y plane) can be important.

This can be critical for some combinations of signals: high-speed clocks, high-impedance inputs, analog circuitry, high current loops, etc.  Sometimes it's just not possible to keep them separated in X/Y enough, and you might have to give priority to some of these signals being on outer layers where they have the ground/power-plane between them and everything else on other layers.