InterSystems Caché Project Files and Folders

cls/My/Deep/Class.cls

I don't think subdirectories should be applied for routines, originally routines aren't supposed to have submodules or subpackages and dots might be part of their name. Also if you need some complexity, you wouldn't prefer using routines but classes to keep things organized.
 

I DO NOT recommend using src, unless you want to mix both back-end and front-end code. 
Or you want to keep the server code in a separated repository.
Here is a scaffolding based on React for better understanding.
my-app-project /
   package.json
    server
          cls
          mac
          int
          csp <- this is our build path, nothing should be added manually because everything is handle by the bundler.

    scripts /

         test.js
         build.js
        dev.js
   config /
         webpack.config.dev.js
         webpack.config.prod.js
         webpack.config.test.js
   src /

         components
               Header
                   index.js
                   Header.js                   
                   HeaderSearchBar.js
               Footer

                   index.js
                   Footer.js
                   FooterCopyright.js
                AppContainer
                    index.js
                   AppContainer.js
          containers
                App.js
           tests
               components

                  Header
                      Header.js                   
                      HeaderSearchBar.js
                  Footer
                      Footer.js
                      FooterCopyright.js
                   AppContainer
                       index.js
                   AppContainer

                              
You can use folders to separate both client and server codes inside the same project. You can even structure your project

using a monorepo approach if you want to keep multiple application modules together.
                  

Now since React will be using webpack's hot module reloading along with webpack-dev-middleware that builds everything within the memory, your Caché server should only work following SPA conventions and providing consumable data.
There's a catch though, whenever the developer builds a new version (using webpack.config.prod), it's mandatory to delete the older bundle and import the project back to Caché to keep the source in sync on the server and the project.