Layouts are difficult if you make them difficult. If you have an idea on how everything in the layout plan, then it makes creating easier. The layouts can go by CSS or if you can keep to a scheme. When layouts get rushed, sometimes fonts won't match, or the color schemes don't seem to mesh well.
Anything is possible, and layouts can be created on any levels. It is not a good idea to try to get into complicating scripting unless you have some experience in that field. But it is always good to know that there is coding and there are a lot of recreated layouts for beginners.
It never hurts to shake things up, or try different things... the good thing about web layouts is that if you don't like it, you can fix it or just start something completely new...
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