My 2 cents.

1) If you want to stay on windows go the .NET 4 route.
- Has great COM interop
- WPF is great for UI (xaml is easy for users to play with, and has great tool support)
- WPF also has D3DImage, so directx interop is handled well (no airspace issues).

2) If you want to go multiplatform, go with QT4.
- Very nice API, makes you wonder what the win32 people were thinking.
- Great opengl interop, which makes it well suited for graphics-oriented apps.
(e.g. Maya, Mudbox, Maxwell, Nuke, Realflow, etc)