The list of incredibly influential papers that got rejected from Nature and Science is long and growing. Conversely, a lot of papers in Nature or Science (particularly in bio) do not necessarily represent deep or groundbreaking ideas, though they are widely cited. It's particularly regrettable the hiring and tenure committees do indeed "punch your ticket" if you have one or two publications in high-profile journals, as this creates (imo) an unhealthy obsession with hyping everything you do into a "breakthrough" result worthy of publication in the top journals. Scientific breakthroughs are rare (increasingly so, it must be) and it has always seemed unlikely to me that there are enough of them per week to fill up three or four prestigious journals.
