How complex were the applications that used those production-grade React setups?

As the number of possible states increases, your vanilla JS solution explodes in complexity when you have to manually define every state transition. The declarative nature of SPA frameworks means all you need to worry about is presentation of your data. If all you need to do is some form validation, then writing an SPA is a terrible idea. If you need to build a UI that functions more like a desktop app with long-lived sessions and complex workflows, trying to manage all of your DOM updates will be a monstrously difficult task. You'll basically end up implementing a slow, buggy version of react.