The default layout is by far the best layout of editing with some re-sizing of the window frames (here is a screenshot of my set-up). The default colours however suck :] The first thing to do is change them. Goto Misc -> Colors -> Maya/Max/Lightwave. Ahh, that looks better. You can customise most of the editing colours under Misc -> Colors. The rest of the interface colours can be changed with a file called radiantgtkrc. Place this file into your d:\GtkRadiant folder and edit (in Notepad) to taste.
The next thing to do is get the tool bar down to a usable size and to change a few other settings. Press P (for Preferences). Under Display -> 2D Display/Rendering, select Display size info. Under Interface -> Layout, un-tick Patch Toolbar, Plugin Toolbar and Wide Toolbar. You will now need to restart GtkRadiant.
I highly recommend reading over the manuals that can be found in the d:\GtkRadiant folder as well as exploring the menu options and other settings.
You are now set-up and ready to map!