Short answer: one should not consider the absolute value of a potential as long as the potential difference drives the ions in the appropriate direction.
The potential difference is needed to accelerate ions in the appropriate direction of the mass spectrometer.
One should consider that in an atmospheric pressure or moderate vacuum ions need to be driven by the electric potential difference towards the MS high vacuum region by a constant decrease in potential (due to loss of kinetic energy through collisions with the gas) whereas in the high vacuum region, there is no need to keep this evolution true as long as the potential difference remains positive relative to the initial (entrance, near thermal kinetic energy) potential.
Just as an illustration, considering a simplified ESI atmospheric pressure introduction with only an ESI capillary, a cone to rough pumping region and a skimmer to the UHV region, one can have:
ESI Needle: + 4,000 V
Cone: + 100 V
Entrance skimmer: 0 V
ESI Needle: + 4,200 V
Cone: -100 V
Entrance skimmer: -200V
The ions will see the same electric field in both cases, as it is the potential difference which creates the electric field and not the absolute value of the potential. There is just one issue: sometimes it is easier in instrument design to have one region of the instrument operated at ground potential (or close to ground potential), and it would be this part of the design which will decide on the absolute values of the potentials that will be applied.