Sometimes it's an issue of alchemy, of pure magic. A couple of seasons ago, Ross and Rachel struck up a romance, but the couple didn't click. But, when Chandler and Monica hooked up, something happened. That's why this fairly unimaginative sitcom premise has worked so well for so long. And it was an absence of chemistry, at least in part, that doomed the rip-offs of those comedies.
Chemistry is unpredictable.
If you had the failure rate in any other industry that you have in TV pilots, it wouldn't be tolerated. Timing plays a big part in chemistry, and so does style. Nowhere is this more evident than in the characters of Niles and Frasier. The actors' timing is perfect, and the styles of Kelsey Grammer and David Hyde Pierce are complementary. The result is a seamless symbiotic relationship.