Of course the challenge is to NOT change anything about gameplay and design, and interactivity, and to still cater for keyboard/mouse fans. We are well aware of that and do not want to make compromises.
I am believer that anything can be done, but I really don't see good coming from this. You can have all the good intentions in the world, but you know the saying... "The road to hell is paved with good intentions".
Eventually you are going to have to change gameplay and design focus to attend to the controller. It will end up having an effect on many systems ranging from inventory design, menu functionality, movement and selection, UI systems, and ultimately game complexity (ie the more skills, abilities and functional aspects of the game you have, the more of a nightmare it is for a controller).
Not to be useless to this discussion, but I just don't see any good coming from this. Sorry.