Only ever have offense primary on offense cross?

Yes, is your answer.

Easiest example that comes to kind is JKA. I run offense set and potency set on him with potency primary on cross. I find that inflicting Heal Immunity on Malak is the most essential step to my success against him, and after playing around extensively, settled on potency primary on the cross over offense or health.

Purely by numbers - yes. The only other way you can have such amount of potency is 2 potency sets. But this way you will lose more offense. The real question is how much potency you really need on that toon.

"Yung_Hen;d-227753" wrote:
Are there any times it’s justifiable to have an offense cross with a primary that’s not offense? potency instead particularly, I assume sometimes its worth it to have protection

I like Grand Ivory Mod Optimizer because it gives me mod combinations based off of what mods I have that my brain just would not fathom. Mother Talzin is the best example to your question. Potency vs. Offense on her are on a sliding scale based off of your own mod options .
Speed set and potency
Offense and potency
Offense and crit set
Potency potency crit
Potency potency potency
All of those are reasonable to put on her. Whether you put potency or offense on her cross depends on where her numbers are. Offense triangle though, unless you want crit.