Eastern Islam.
Diamond:
I'm not too sure of all the details just yet, but the main POD is the Arab victory over Byzantium in the 7th century. After that, the muslims turn their focus towards the east, however. By 1000, most of Asia is Islamic, and the religion has begun to make inroads into China. Islam acts as a unifier for the various Turkic and Mongol tribes, and they conquer China in the 12th century, before going on to smash Japan. My thinking is that they never turn towards Europe in this TL. Japanese, SE Asian refugees and the random Mongol expedition discover North America, and Old World diseases begin to spread among the native population along with Islam. By 1500, several khanates are formed, most notably that of the Lakhota, which benefits greatly from trade and advisors from the Chinese colony around Seattle.
Meanwhile, in Europe, the Visigoths in Spain experienced something of a revival starting in the 8th century - the Arabs never made it across all of North Africa, never mind into Europe, and Hispania begins to become the cultural and scientific powerhouse of Europe. The Pope flees to Toletum in 955 after an abortive invasion of Italy by the Abbasid Caliphate, and the city has been the headquarters of the Church ever since.
Shut out of the east, Christianity has spread instead into central and northern Europe (the Norsemen were mostly converted by 1100), and deep into western and central Africa - fiercely Christian Berbers traverse the desert sands in this TL, and missionaries have spread the religion deep into the Kongo Basin and beyond.
A union of trading and mercantile cities in the Low Countries and Germany, the Hanse League (much akin to OTL) springs up in the 12th or 13th century, uniting the region and becoming wealthy by acting as a center of trade and learning. Some of the finest colleges in Europe are found in Hanse cities.
By 1500, Hispania's ruling Gothic family is inbred and mostly powerless; the Church has ruled in all but name for the last century. In 1520, they legitimize their power after the last king dies without an heir by declaring Hispania a Holy Realm. Over the next century other southern European states join, either through diplomacy or conquest, forming a powerful Holy Union.
The Americas are discovered (by Europeans) in 1560, and the Union, flush with its new power and missionary zeal, are quick to colonize Central America. The Hanse and Norse jump on the colonizing bandwagon and found colonies of their own in northeastern North America and along the northern coast of South America. Other, minor states, like England, Neustria, and Austrasia, have trading outposts sprinkled all over the globe.
Now, in 1600, the forces of the Holy Union are beginning to turn their attention back to the long-neglected Egypt, Middle East, and Balkans, where the Abbasids have held sway for centuries. The first blow in the this conflict has already been struck, in fact, with the successful Hispanian invasion of Greece in 1593...