I just migrated my current React project, which is not yet that big, just over a hundred files, and it was actually very easy because I used create-react-app and it offers great support for the language.
It took me like 5 days to rewrite my components and data layer. There were some challenges, specially a couple of React contexts, but here I am!
It feels like my browser got more intelligent. It's way easier to make a big refactoring, which usually happens a lot in the early stages of a project.
If you struggle with complex projects in ES6, I commend you to try Typescript (or you could actually also try Flow). Static types can give you a lot of confidence and make your work more easy.
But please, be sure to understand how the type system works in Typescript. It's very nice and flexible but different if you come from other languages with static typing. For instance, I work with C# on the backend and it's just not the same thing: Typescript mounts a static type system over a dynamic language. It's very nice, and more flexible, but different.
What languages are you currently enjoying? I would like to know!