The main thing that can cause shit to hit the fan is not properly handling errors. I highly suggest using domains, and that when an error occurs, if you can, that you gracefully exit. If not, then all other requests will just abort and that isn't very user friendly.
You will also want a way to be notified of errors, so you can stay on top of them and fix them right away. I use winston and have the error level set to email me.
If you want to talk in more detail, contact me... address is on my profile.