Adobe Air should be the one for you. It creates a desktop app which is basically a webkit wrapper. Then with that, you can build your app straight in HTML, CSS, JS or even Flash. It has a few set of JS API which you could learn for native operations like file access and more.
Recent versions of AIR prepackage the runtime with the app, which makes your app stand-alone and will not need the AIR platform installed on the target client.
For easy development, Aptana Studio 2 has a plugin that helps you in developing AIR apps and automates much of your AIR app building like package compiling, app previewing etc. It's quite outdated though (AIR 1.5 and AIR 2 beta) and you might want to update the SDK. Also you could Google around on how to tweak the compiler options to build a stand-alone app.