I doubt any of you can honestly tell me that you don't judge books by their covers. We humans are creatures that often rely on vision as one of our most prominent senses, and before we actually get to know any other people we instantly make assumptions about them with out even trying. If we instantly make assumptions about people, it's very likely that that judging books by their covers is not an evadable thing.
The first thing that people might look for on a cover (besides the title) would probably be whatever is being centered upon on the cover. An example is the cover to the right of Ally Carter's Don't Judge a Girl by Her Cover (See how I incorporated the book's title with the post, wink, wink) On the cover the main highlight is the girl in a school uniform which (assuming you didn't know what the story was about) instantly gives an impression of a school theme. Depending on what your taste in books are this might be either intriguing or an excuse to say no to the story.
Covers that are not as clear can give a very confusing idea to those who see the cover, therefore making it so some of the audience who may enjoy the story very much not read the story. The cover of the book on the left, as well as the book's title might give some the idea that this book is a young adult romance which takes place in Italy. Though that may be the case, it is my understanding that Lauren Henderson's Flirting in Italian is more focused on a mystery that takes place in Italy (with some romance on the side) I think that covers, and titles for that matter might be given a slightly misleading look to try to appeal to a broader audience.
I once asked an author weather or not they got to choose their book titles and they told me that it really depends. She was an author of many books and she had come up with the titles of about half while the other half were chosen by people such as people helping her get published.
Covers can also drive people away from reading a book no matter how good the story may be. Covers that look homemade, Photoshopped, cheesy, bland, etc. could easily turn away audience members. These types of covers are completely a readers opinion, and those who are not as judgmental about covers would be more likely to pick up books such as these.
And now the final question, can a judge a book by it's cover. Yeah. Sure. Why not? I encourage you to every once and a while try to take a look at a book that might not have a very appealing cover to give it a chance, but like I said before, being judgmental is part of being a human. There really is no way not to judge a book by its cover.