This is how I got DNF to run:
Step 1) create a new WinXP bottle and install Steam into it.
This will take care of many of the dependencies that DNF needs.
Step 2) register yourself with Steam.
Step 3) Install DNF from the DVD. It will at some point invoke steam and will happily proceed if you happen to be logged in. It will then download the real game (6GB) from the steam network.
At this point attempting to start DNF will fail with the by now famous dinput mouse issue.
Step 4) start regedit within your Steam+DNF bottle.
Step 4a) In the Registry Editor browse to HKEY_CURRENT_USER/Software/Wine/Direct3D (if you don't have a Direct3D key, there, you'll need to create one), and add a new String Value. Set the name as "StrictDrawOrdering" and the value to "enabled".
Step 4B) browse to HKEY_CURRENT_USER/Software/Wine/DllOverrides
if there is no key dinput8 in there, create a new String Value "dinput8" and set it to "native, builtin".
If I now start the game through Steam, it will play the full intro and allow me to start the campaign.
It hangs during starting the campaign. Will post more once I get further.