Tailor both the resume and cover letter. How many times have you heard people say they customize their cover letter, but send the same resume to everyone? Usually they are very proud of themselves for doing this, as many job seekers send one form letter and resume to everyone. Unfortunately, when a resume is competing with 200 to 400 others, it has to stand out from the crowd. Recruiters don't have time to separate the "diamonds from the dirt" in the 10 to 60 seconds they spend skimming for relevant experience. It is the candidate's responsibility to sort the valuable stuff from the extraneous, using only 20-carat material to land an interview.
Replying to all resumes would be the polite thing to do, but often it simply isn't practical. If a company receives 200 responses for an ad, or experiences a continual deluge of unsolicited resumes, it would spend an inordinate amount of time sending acknowledgments. If you really want a receipt for your resume, send a stamped, self-addressed postcard asking for one. If you make it easy, the human resources department will comply.
A great resume can get you invited to the penthouse, where your masterful interviewing techniques will lead to a great opportunity complete with a substantial raise and a covered parking spot with your name on it.