1. what is it that the site wants me to do there?
2. Does the site's design reflect that?
For instance, when I go to Google, there's no doubt they want me to search - and they make that abundantly clear from their design (i.e. just a search box, with not many more options). Take their competitor Yahoo though - what is it they want me to do when I go to the home page? Read news? Check email? Search? Local? I'm not really sure. To be honest, I'm not sure they know either.
Other examples: my old friend Perez Hilton makes it pretty clear that I am supposed to check out the pictures on his site - in fact, he even doodles on top of them to draw my eye to them further, having a sort of highlight effect. A well designed news page clearly tells me that I'm supposed to click on an headline, while a poorly designed one tells me I am to.......do what?
So how do you tell if your design is telling the user what you want them to do? I deploy the Markson squint test - I look at the page and squint my eyes so that everything on it is blurry, and then I look to see the shapes/ sizes/ colors that stand out from the rest. If those prominent pixels match up to what you want a user to do, you're in business. If not, you've got some work to do.