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When you submit to someone, be it an editor, or an agent please remember that this is the first thing they see of what it is like to work with you. Even if they know you personally, have enjoyed talking to you at a convention, or are the parent of their child's best friend, none of those is a professional relationship. Please note the "w" word, its important. While the author - agent and author - editor relationships are a bit different from the way that members of the same engineering team, military unit, or even coffee house staff will relate, they are all business relationships. There are numerous things that go into making any working relationship a good one. Liking the person isn't necessary, nor is sharing the same pastimes. On the other hand, knowledge of the field you are working in is important, and competence is key.
Paramount above these two virtues and probably all others of a working relationship is professional respect. This does not mean you have to worship the ground the other person walks upon, or sing peaon's to them daily, it just means doing the little things. So when you submit to someone, and you've ignored, or not bothered to even read the submission guidelines; what does it say? It says you don't have any respect for that individual's professionalism or their abilities. Now the person picking up or downloading that submission is forming a, usually accurate, opinion of you. Where they ask for twelve point Times New Roman, and you've used fourteen point Courier you've achieved strike one. When they say double spaced and your novel is single spaced you're at strike two. If your cover letter starts with 'Dear Sir or Madam' or perhaps 'To Whom it may concern', when the submission guidelines clearly state the persons name well, I can count to three.
The nice thing about being the agent or editor is that we don't have to put up with people who do the equivalent of showing up for a job interview (in the simplest terms that is what a submission is) that looks like they rolled out of bed after too little sleep, too many potables, and wearing the same clothes they attended last nights outdoor concert in. We can simply say “Your work does not meet our needs at this time." and be done.
Do you want to work with anyone who doesn't respect you?
(edited to correct one or two things)
Second edit
[Note to self, don't try writing or editing anything quickly in a bad mood.]
