I re-read 'The Lies of Locke Lamora' recently, and I'd argue the central trio is really Locke, Jean, and Father Chains. Chains sets everything in motion, training Locke and acting as a moral compass even after he's gone. Without him, the Gentlemen Bastards wouldn't exist. Then you've got the dynamic between Locke and Jean, which is the absolute heart of the story. Their friendship is the engine.
Calo and Galdo are great, but they feel more like a unit and less like individual drivers of the plot. The Falconer is a compelling antagonist, sure, but he's not central in the same way. A lot of the book's soul is about the found family within that gang, with Locke's reckless brilliance bouncing off Jean's steadfast loyalty.