Read the manuscript after you have set it aside for as long as possible. Six months is ideal but give it at least a month. This distance is essential to effectively edit your novel manuscript.
Concentrate on the conflict in your novel. Ignore grammatical errors and typos. As tempting as it is to correct these now, you must focus on the most important element in your manuscript. Readers won't get very far if there is no conflict.
Pay attention to the pacing of your story as you read through it the first time. Concentrate on how you build suspense. Conflict, tempo and suspense go together. When one is flawed, the others suffer too. Fix these problems before anything else.
Focus on your characters once you've determined the conflict and suspense are there. Character development is no less important than the plot and in some novels, even more important. Make sure the point of view is the most effective one for conveying this story.
Notice the voice in your novel. A timid style isn't usually appropriate for a thriller. Biting cynicism doesn't go over well with romance readers. Decide what the narrator's attitude is to the conflict and characters and match the writing style to that voice.
Look over the manuscript for grammar, spelling and punctuation errors only in the last revisions. These aren't as important as conflict, suspense, characterization and voice, but they're still essential in conveying a professional image.
Hire a professional to edit your novel manuscript. This is especially important if you're self-publishing or tapping into print-on-demand technology. Be sure to choose a reputable book doctor and clarify what she'll do for the fee (see link in Resources for advice on this).