Yeah, it's been a while since I've been in a high traffic situation, but back in the late 00s we had a couple sites with 3-5 million daily unique users. Each site had a single master, a couple read replicas, and some queries were cached in memcached.

The problem in MySQL we eventually ran into was the read replicas fell behind master during peak load (by 30-60 minutes depending upon the day). So we still had to hit the master for certain queries. I left before we took the next step to fix this issue.