Beyond the size of the user group, are there any other specific that a designer needs to keep in mind?
What is the biggest difference between working on a small department application and an enterprise level application?
Scope creep is probably the biggest difference between the two. Often in a small department application you have a fixed roadmap and vision for how the product will be developed, and you can execute to completion.
With an enterprise level application, often times there are complexities or requirements that arise during the development process, especially when you go into alpha testing. Those issues can lead to scope creep, which can affect the overall deployment of the application.