There's actually a very scientific way to do it, but I think it's a little deep for me to explain here. My best suggestion at this point is to first decide what you want the site to be about. Everything you do within this site should be related in some way to that unifying idea. Similarly, everything designed for that site should also be somehow linked to that idea. Next, start experimenting (sketching) ideas for what you want the site to look like. What you want to get from this, ideally, is a grid system. A master grid that determines rough size and shape of each frame, and grids within each frame that determine the placement of content. After that I would suggest selecting fonts. Select one for headlines and titles that compliments any logotype if you have it. Select another, clean, legible, and deep family of fonts to use for all the body text. (In this case you probably want a family of fonts that is easy to read at smaller sizes, and is designed with light, book, medium, and heavy weights as well as italic, and bold styles. Simply clicking the bold or italic button to change a typeface mutilates most words, as the font was not designed with this in mind.) The actual style part is entirely up to you though.