To use R2 you’d need to host images/assets separately on their own domain rather than just put a CDN infront of your entire site and forget about it. Putting assets on their own domain isn’t uncommon but for some stuff it can be a big inconvenience with build pipelines/software support.

I’m not sure on R2 specifics but I remember when I wanted vanity names on Cloudflare I.e assets.example.com it was not possible unless you give Cloudflare control over your entire domain, dropping your current nameservers or sign up for an enterprise plan for cname support.