If you haven't read anything by him, I'd start with In the Name of the Rose. The beginning is a little tough to get into, but if you persevere you are amply rewarded (in the afterwords it is disclosed that this was a deliberate literary choice, I won't spoil it by explaining the rationale, but it does make sense). Foucault's Pendulum is the magnum opus.
Edit: after In the Name of the Rose I'd probably go with Baudolino, but FP is a valid choice as well.