Most people constructing websites don't fully appreciate when you're doing page layout, you're doing it for humans. Sure, in some vague sense designers understand the users are 'out there,' but not the implications for code. CSS is often the primary tool for
interface design, which means the rules for human-computer interaction design apply.
Unfortunately, few CSS-based developers know Fitts' or Tessler's or Hicks law, how the variety of interaction design principles interrelate and modify each other, or really anything about interaction design.
Fitts’ Law: The larger the target object, the faster it can be acquired.
Fitts’ Law and Text Links gives some practical CSS implications for Fitts.
Link presentation and Fitts' Law starts to get into the real implications for navigation.
This
mezzoblue redesign with Fitts' law in mind is a very nice explanation of the human-computer interaction design thinking which should go into CSS based layout design.
Without the grounding in interaction design methodology, the web designer's default of "if it looks cool -- do it" does not produce the best result for users. There are a variety of interaction design principles, some which modify others. Understanding interaction design priciples -- along with the implications for coding -- can make you a better CSS designer.