Bf-110 had the advantage of having all weapons in the nose, its burst is much more accurate. Also, it has gunners at its back. Fighters that can shoot forward and backward is dangerous. As with many big heavy planes, they are slow to accelerate and controls are sluggish at low speed. Although having high top speed (for 1940-41), they are vulnerable at low speeds and its big size means it cannot maneuver very well in tight space between bombers and other planes during escort mission.
20 mm Hispano-Suiza equipped Spitfire Ib/IIb/Vb is deadly, but unlike that guy's signature from "Pearl Harbor" movie, it suffered from buffeting and will throw its aim outwards when shooting that cannon. But nevertheless, that 20 mm cannon is dangerous, both in real life and in game. In game (Il-2 at least), it will make a big effing hole in the wing, and throw tight-turning enemy plane into deadly hard-to-recover spin.