Defeat a shardbearer boss to obtain a Great Rune
Rest at a Site of Grace after obtaining the Great Rune
Go to the corresponding Divine Tower
Activate the Great Rune at the top of that Divine Tower
Rest at a Site of Grace again
Open the Great Runes menu
Select the Great Rune you want to equip
Use a Rune Arc to activate its effects
Repeat with another Rune Arc after death or when the effect ends