According to high-powered recruiters, here are the three biggest mistakes that will get your resume thrown directly in the garbage:

• You Don't Meet the Basic Requirements – Make sure you check out the requirements listed in the job description and show immediately that your skills and experience are a match.
   
• You're Not a Culture Fit – Companies are looking for candidates who are a "cultural fit,” not just someone looking for a job.
   
• You Don't Pay Attention to Detail – Make sure your resume is easy to print, easy to read and has a cover letter addressed to an actual person. “To whom it may concern” isn’t going to cut it. (Mashable.com)
• Plus I've seen a boss or two toss a resume in the rejection pile because of poor punctuation, folded resume's and handwritten (sloppy and otherwise) envelopes.
• I've heard of a new trend of video resume's. Unless you have some serious video production skills or a tone of cash to hire it out, don't bother.  Stick to the tried and true paper resume', just follow the above suggestions.