I've used FR for my two longest running 5e campaigns: ToD and OotA, both heavily modified. Until 5e, I stayed well away from the Realms, but I inherited the ToD game from a friend and decided to try out my first Realms campaign. In both games I pretty much ignored canon and treated the setting as my own. The actions of the PCs drive the game and I've adjusted he levels of the NPCs and world at large to be more inline with Eberron's expectations.
For example: in Rise of Tiamat, I took the fact that the factions were willing to work together to stop the Cult of the Dragon to mean that the threat it posed was UNPRECEDENTED. Why else would the Lord's Alliance, Harpers, and Zentarrim work together? The devastation caused by hundreds of chromatic dragons, driven to murderous rage by the Dragonhorn and Tiamat's return, ravaged everything from the Sword Coast to the Sea of Fallen Stars. Forests burned, waterways were poisoned, evil humanoids came out of the woodwork to exploit the destruction, and undead proliferated. The heroes might have stopped Tiamat, but ruined countryside led to a refugee crisis in big cities like Waterdeep and Balder's Gate. Famine, pillage, banditry, and the like plagued the Realms. And then someone summoned every demon lord from the Abyss into the world...