Tim Brown: More Perfect Typography
A geeky approach to layout and typography - full lecture on Vimeo.
Basically it boils down to picking two numbers - one, say, the base font size (which should be picked to suit the font), and one from another site element (say the width of the images, or the viewport of a mobile phone, or something).
Anyhow, that’s it - any number you need in your design (line-height, paddings, any widths, heights, etc) you pick it from this list. Et voilá, instant great layout. Well not quite, it all still depends on your design skills as you can see from this blog.