MOST people are used to 2 decimal place currencies. So by your own comment, they need to be considered.
Yes, everyone needs to be considered. The only clean solution here, to make it right for everyone, is to hide the ISO 4217 code in the back-end whenever possible, and display to the user whatever their locale settings are. The average wallet software should allow this kind of flexibility.
This way the ISO code would become a pure technicality for low layer applications.
^ Everything here is sensible ^
It makes sense to use the same unit as used in the blockchain / by the protocol then, doesn't it?
No. The purpose of an ISO is to help make bitcoin amounts easily represented in the world's non-bitcoin, existing, mainstream/legacy financial/accounting systems.
A 2dp code achieves this best. In fact, 99% of them expect it.