I think Zendesk has a nice balance of configurability. For a person skilled with .css and code there is a lot of flexibility in building the front end of the site.
On the admin side, one can easily create custom views and setup layouts of tools and extensions to the agent interface.
There are still some limits however. The automatic dashboard that is displayed to agents cannot be configured away from its default layout at the present time. So if you don't want to use the native dashboard, you will have to tell your agents to ignore it and use a custom view instead. You cannot set a custom view to be the default dashboard that shows up when you log into the agent interface.