Being a hiring manager gives you insights into the hiring process that are impossible to attain as a job seeker, no matter how many resumes you write or how many interviews you are invited to. Why didn't you get the job? It's not always the painfully obvious stuff that you read about in interview horror stories -- showing up late, drunk, or taking a cellphone call in the middle of the interview. You don't need to arrive wearing sweatpants or make inappropriate jokes to get a thumbs down in the first 10 minutes.
Recently, at the Golem Technologies blog, Charlie Balmer summarized the top issues that will lose you a job offer, and based on my own experience, they are spot on. Recently, for example, I had to hire someone for my own team, and I had 200 applicants for a single position. In a situation like that, it's critical to develop methods for rapidly reading candidates, or you'll spend the rest of your life trying to find the right person for just a single opening. If you're in the job market, pay attention to these critical issues and you'll improve your chances a hundred-fold.
Trim your resume. If your resume is more than two (printed, dead-tree) pages long, it's too long. Your accomplishments should be tightly edited blasts of information, not verbose or rambling paragraphs. The rise of online resumes doesn't give you permission to waste HR and the hiring manager's time, and the rule of thumb that no one looks at your resume for more than about 30 seconds still holds true.
Know why you like your current job. You should be able to clearly articulate what it is about your current role (or your last position) that really excited and motivated you. You should understand what drives you, and be able to talk passionately and articulately about that. If it seems like you don't care, have no passion, or are just looking for another paycheck, the hiring manager will pass. He or she needs someone who loves what they do and will thrive on helping the company succeed.
Have real-life anecdotes. You'll get questions about how you handled particular situations in the interview. Know yourself and your own job history well enough that you can recount examples from your own work experience. If all you can talk about is what you would do in the future, it won't instill much confidence.
Have the skills listed in the job description. Or at least be honest that you are trying to change roles and are willing to take a more junior position to learn and grow. Bottom line: Don't mislead the interviewer about skills you don't really have or experience you haven't yet accrued. And arrive prepared to do some hands-on work, just in case you're asked to work through a problem, project or situation that is representative of the role you're interviewing for.