Client-side web programming (HTML, JavaScript, CSS) has improved greatly in recent years. You could make a reasonable argument that this is the best environment for building user interfaces today: it's quick, it looks decent, there are tons of libraries and stylesheets available, and the developer tools are quite good. Firefox even has a 3D Inspector view these days — if that doesn't convince you, I don't know what will.
Meanwhile, node.js has become a reasonable platform for server-side JavaScript that interacts with the outside world. Node provides libraries for accessing the filesystem, making network requests (not just HTTP), and running arbitrary processes. And it has over 25,000 third-party libraries to help you out.
This environment already makes sense for building local applications. You'd run a node.js server locally to handle interaction with the outside world, and you'd load up a web page in your browser to provide the user interface. Your browser and server would communicate over HTTP requests as usual. Hide the browser's toolbars and it doesn't even look out of place.
The node-webkit project takes this one step forward: it integrates the node.js libraries into a Webkit environment. So now instead of splitting your local application into a server and a client component, having these communicate over HTTP, and having to launch these separately, you can structure these applications in a much simpler way. There's no HTTP involved: your JavaScript just acts on user input directly, calling into node.js libraries when it needs to.
I've been playing around with node-webkit a bit the last few days, and I must say I'm impressed with how productive of an environment it is to program in. The number of JavaScript libraries out there really makes up for the ugly bits of the language. I feel like I've been shying away from building graphical applications because of the overhead of doing so with something like PyGTK; I think node-webkit might change this. Node-webkit applications require so little boilerplate that this approach makes sense even for one-off scripts where you'd like user interaction.