Two very different things happened in this region within about a century and a half of each other, and both are consequential far beyond it.
The first is the papacy's residence at Avignon. From 1309 to 1377 the popes lived not in Rome but on the Rhone, in a fortified palace that still stands, under heavy French influence. The period is conventionally called the Babylonian captivity by its critics, and it produced a large and efficient papal bureaucracy, a great deal of resentment about taxation, and, when it ended badly, the schism of 1378, in which rival popes at Rome and Avignon excommunicated one another and Europe divided along political lines for nearly forty years. The conciliar movement, which argued that a general council outranks a pope, came directly out of the effort to end it.
The second is textual. The Sefer ha-Bahir, the earliest work of what became kabbalah, appears in circulation in this region in the later twelfth century, and the circle around Isaac the Blind in Provence is the first identifiable group teaching the doctrine of the divine emanations. Gershom Scholem's reconstruction of these beginnings placed the movement's emergence here before its development in Catalonia and, much later, in Safed. The region's Jewish community was also a major centre of philosophical translation from Arabic into Hebrew.