You can customise the gui in any way you want. The difficulty of doing so varies with the tasks - so if you just want to change the skin - that is pretty trivial. You would just create your own copy of the control prefabs, assign your own sprites / fonts to it.
If you need to create new GUI elements, it
can work with Unity GUI, but thats a completely different system with a completely different programming paradigm. It might be easier to customise tk2d UI for it, but maybe not. I can recommend something if you have a more specific question about what you need to do. tk2dUI is meant to simplify the most common tasks in games, e.g. menus, buttons, sliders and so on.
The back end isn't commented and can get quite complicated, but feel free to post here if you're stuck, we're always happy to help