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My thought is that one of the biggest mistakes I see in fiction is the over-use of the comma. It's a subtle piece of punctuation and needs to be handled with subtlety. There are those which are absolutely essential and can't be missed and there are others which can be used or left out to fit in with the writer's intention and style; the former must be present, the latter would be optional. Too many commas will slow a piece down. Slowing a piece down may or may not be desirable, depending on the context. To me, the use of puncuation can, as you hint at in your title for the thread, be flexible within the general parameters of the rules. I think it was mentioned earlier that the odd misplaced comma will not put off a reader. I agree with that. It's also true that complete misuse is likely to turn a high percentage of readers away, unless you're working with something that has a style all of its own (where you'd have to be exceptional to pull it off).
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