Famous motorcycle racer and builder Andreas Georgeades has been building motorcycles with unique engines for a long time. His custom motorcycles have used engines from a Ferrari Dino V6, a Ferrari 308 V8, a supercharged Ferrari Dino V6, and a V12 made from two Honda CBX inline-six engines.
His current project involves taking four Yamaha YZF600 599 cc inline-four engines and building one 2396 cc H16 engine. The basics of the engine is two inline-four engines are connected to form a flat-eight engine. Then both flat-engine engines are stacked on top of each other with the gearbox between them.
This video does a good job of showing the design and layout.