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Qt is the best cross-plataform GUI Toolkit.

But it still feels odd on Windows, and OSX, and Linux (provided that most Linux users are on Gnome these days).

I would rather spend twice the time coding it for native Windows forms and OSX Cocoa.

Provided enough resources I think the best approach is writing a library in C/C++ for the core and then using the native toolkit for the GUI.

Transmission does this and it's beautiful both on OS X and Gnome. Adium does something similar and it's a good mac app.