I disagree with Ewwwww on the long-running series thing. It seems to me that, especially when you read it in one sitting, a series is funnier than a couple of split comics, because you bombard the reader with a succession of jokes.
Of course, always make comics that can stand alone, even if the punchline isn't horribly great. A series where the joke doesn't come until five strips later probably is a bad thing.