Language is probably the biggest one.
Others would certainly mention the wheel, medicine and electricity as extremely significant. However, I also believe that one thing which may not be mentioned quite as often as other notables would be war. Wars have very significant effects on the participants themselves of course, but on a larger scale they can change the fates of nations, continents or even the globe itself. Let s take World War II for example. Most people today probably don t wonder about such things very often and simply take the events we know to have occurred for granted, but I believe that the status quo could have easily been radically different.