Many will probably call foul on this one, but I personally like the Tk toolkit quite a bit. It has bindings in many popular languages (Python, Perl, Ruby and obviously it native Tcl). It recently had a facelift which improved it's appearance under Windows and Mac(now native looking on those platforms) greatly. On Linux its still looks very much like X11's Motif out of the box, although slowly they are trying to get native GNOME and KDE themes.
It's a lightweight and easy to use GUI toolkit, that has a couple of very powerful and interesting widgets(Canvas, anyone?).
Just a recommendation, but I agree with ShiftPlusOne the decision depends on what language you're using and the target platform.