As you may know there was a lot of debate if the expansion after MoP was going to be a burning legion expansion or an island expansion as from a lore perspective they made more sense than WoD prior to War Crimes. There are more possibilities like an expansion where Bolvar aka The Lich King is the main antagonist or maybe even Murozond as he died in a reality we prevented from happening. Had not Malygos proven what the people of Azeroth could do the titans would have destroyed Azeroth in Dawn of the Aspects and Alganon nearly destroyed Azeroth as well in WotLK so it might be a renegade titan group other than Sargeras. Who knows it might even be exploring some unknown secret of what lies beyond the unexplored sea west of Kalimdor and east of the Eastern Kingdoms, if WoD has taught us anything it's that guessing at this point is rather useless.
As for which is the most significant war I would say is the war of the ancients. Just think of how many characters died there, Sindragosa, Broxigar, Malorne and so many more. Not to mention Illidan got imprissoned, Neltharion became Deathwing, the pandarens split from the world and the Naga were born.
