I've just recently gotten back into GUI's myself, after a 20 year lull. Back then, it was Linux with GTK2, GTK3 and Glade were pretty new and a little too flaky to be worth the effort. Now, just a couple weeks ago, I found myself wanting to throw together a small Modding GUI toolkit for a friend who's, well, not the most technically minded.
So I started with what they already have installed, Python and Tkinter... Well, that was a horrendous experience. The Python->TCL->TK hop-skip-and-jump routine is, frustrating, and at the end of it, TK's not exactly the most capable of GUI's. Don't get me wrong, I love TCL, it's a fantastic language, I was very deeply into it back in Uni, getting into the guts of the language. But TK... While it kind of works in TCL, it's frustrating as heck in Python. Take for example, checking to see if a tree item is hidden, it returns a '0'. Not the number, it returns it as a string. If you forget to explicitly cast it to an int, you get True (in TCL, it's a number with a string representation, and it'll use it as a number in any numeric context, but when translating it to Python, you just get the string rep). As for the other Python GUI options, both myself and my friend are presently in Windows and, well, getting any of them to actually install cleanly was... problematic. And if I had trouble getting those toolkits to install...
So I started looking for better options. And I came across one I think well worth mentioning. GtkD. D really is a better C/C++ (I remember being rather disappointed when Dave dismissed it as merely C++ == D naming silliness, seemingly without actually looking at the language itself); it's an absolutely beautiful under-rated language, IMHO, which pretty much covers the useful parts of C#, without feeling like the proverbial "everything and the kitchen sink" that's all too common with Microsoft frankencreations. And paired with GtkD (which has a few minor gaps still, but nothing serious) bringing with it GTK3/Glade, has been a comparative delight to work in. I did miss GTK, but I didn't miss C (though it was certainly educational in the ways of OOP back in the day), and this combination is just delightful.
Now, I'd rather be using Dgui, I'm pretty sure it would be far more effective, rather than GTK through a layer of D wrappers (where all that CTFE goodness is very little to chew on), though when I was poking around for options which just work so I could get on with re-implementing that toolkit, it was throwing page fulls of errors with the basic Hello World example, very little idea what the problem was. Plus I don't think it had a GUI builder, though I think there may have been something to do with Visual Studio — which I'm not using (gvim is my present IDE at the moment). But, I needed something I could get up and running with now, and more importantly, that just worked for my friend, too. I'll have a look at Dgui again later, because I'm sticking with D for my personal projects now, but GtkD was the easiest option to get going in again; partly due to my prior familiarity to GTK, and I just had to give my friend the GTK3 runtime installer, along with my compiled binary (a shared Dropbox folder works wonders), and they were good to go.