The mutation leading to Y. pestis never happens.
While it was not the only cause for "the black death", and there have been other plagues, it is probably the single most influential thing in recent human history. And there is nothing that says there would have been other plagues in its place. And while the invention of metallurgy, or other similar inventions, have on whole a far bigger impact, they were not singular instances. Bronze working, for example, were invented in more than one place. The mutation that lead to Y. pestis were most likely a singular instance, and if a meteor happened to hit the area in that timeframe, then world history would have changed quite a bit.
Y. pestis is a rather ineffective disease, which makes it a good candidate for a killer.
Another fun virulent what if, is to switch smallpox (the biggest cause for the rapid decline of the native American cultures) and syphilis (came from the Americas). That would have disabled the Europeans for some time (hell, it pretty much single handed killed the Mississippian native cultures)