Do your research. Read the book thoroughly, but also find out what you can about the author and the era in which the book was written. Determine if this is relevant to the impact of the piece.
Take many notes about the content. You can use these notes for ideas on how to guide your meetings.
Consider the setting of the book--the location and time in which its events take place. If the work is a period piece, think about how the time was represented.
Consider major themes and motifs. These will comprise one of the biggest areas of discussion at any book-club meeting.
Examine the characters in the book. Ask yourself if they were realistic, likable or emblematic of a greater idea. Consider specific points in the story that lead the reader to think a certain way about each character.
Consider the plot and/or subject matter. Focus on what stood out and how the story began and ended. Decide if the conclusion was well-defined. Analyze what the book "means" and why it was chosen for your book club.
Come to the meeting prepared with your notes and discussion questions. However, don't feel you need to cover all of them. Use them as a guide, not an itinerary, and allow for a free-flowing exchange of ideas. Pose the most salient questions to your fellow book clubbers, and give them plenty of opportunity to talk.