I guess there's just a degree of prediction and intuition involved. For example, making a website that *relies* on Javascript is one huge error since a healthy portion of people do go around with it disabled. Yet, I still see many sites designed in this way.
With web design it's best to just try not to be too fancy. If you do, do it in a way that's guaranteed to work for most people. Using crazy javascript/ajax/flash navigation, galleries and whatever else may seem like a good way of standing out intitially, but a lot more people would just prefer that you stick to conventional ways of doing things as they like to use the same browsing techniques across all sites that they visit. When one site such as Snarkpit suddenly has popup screenshots which forcibly throw new, resized windows at you, it stands out. But not in a good way.