Mozilla looks like an interesting platform. Robert has been evangelizing it for a while; I just started looking yesterday, after downloading Komodo and seeing what it's made of.
It is a huge project. As well as the browser, it has mozdev, its own little mini-sourceforge, with 71 (at last count) projects, including Mozilla-based browsers, language bindings, development tools and mini-applications.
Using Mozilla as your application framework introduces quite a bit of bloat right from the start. However it's not as much as you might expect. The runtime zips down to about 10 MB (including everything - you'll want to remove mail and news) and the VM size of a single-window application on Win2K Pro was about 12 MB for me.
Compared to .NET apps, this is both better and worse. A single-window C# app will use about 15 MB of RAM but will produce an extremely small distribution archive. However the user must have the .NET framework installed, which is a good 20 MB to download.
The best compromise I've seen so far has been coding in C++ with wxWindows, which results in distribution archives around 1 MB and a VM size of about 2-3 MB. Coding your UI in C++ with wxWindows and using Python for the higher level logic adds about 500k to the distribution archive and about 1 MB to the VM size, which is not bad at all.
However, if you're writing a decent sized application (an IDE, for example!) and the extra bloat is not that much of an issue, XPToolkit may well be worth considering..