Well, both the Spitfire and the Me 109 were definitely "long in the tooth," and I doubt there was much more to get out of them without a major redesign. Both designs could have been revised and I believe the Germans made a virtual air force of Me 109 variants for one reason or another, including one with inward-retracting, conventional landing gear and another with tricycle gear.
The 109 needed elevator, aileron and rudder trim, inward-retracting landing gear, better aileron design, a bubble canoy, and more fuel. It COULD have had all. The Spitfire could have used wider gear, a less draggy radiator setup, a more swept windscreen, and more fuel. If could have had all that, too.
In the end, neither "improvement" would likely have changed the war's outcome, so how badly were they needed? Apparently not that badly. I know it is a simplistic view but, in the end, both were good enough to finish the war. Had the Germans won, the Me 109 would have been there at the end, too, as it was in defeat. Ditto the Spitifre the other way.
Back to the subject of the thread, I believe the real life fastest piston twin that was a production model wasn't likely faster than about 435 mph or so ... the rest being either paper designs or prototypes that weren't ever serially produced. The Hughes XF-11 and Twin Mustang were both post-war, though firmly rooted in WWII. They built fewer Do 335's than they did Ta 152's, so I discount both of those as non-events. Depending on who you believe, they only flew between 16 and 22 examples of the Do 335 before the war ended.
So, if we discount the fabulous prototypes, we are left with very few real production fast twins from which to choose. left to my own devices, I'd take a Tigercat since it actually made fleet service entry prior to the end of WWII, but obviously never made it to Europe an didn't contribute to the outcome. If I discount the Tigercat (I won't fight too hard since it was a non-factor in the war), then I'm pretty much left with the Mosquito and the P-38 as meaingful twins. For a fighter, I'd take the P-38 any day of the week. If range and bomb carrying capacity were important, I'd take a Mosquito except in the South Pacific due to the deleterious effect of tropical weather on wood airframes.
I think all the rest were not as fast as either the P-38 or the Mosquito and were not produced in large enough numbers to warrant consideration as a WWII service twin.
I'm sure there are those who believe paper airplanes that were deisgned but never flew are valid for consideration along with the one-offs. If you are one those, choose in peace ... no argument from me at all going forward. Went back and read some of my earlier posts in this thread and I must say they sounded a bit pompous. Didn't intend to come across that way at the time but apparently did. So, as I said above, no more arguments from me. I'll express my own opinion and not argue about anyone else's ...
Fantasy airplanes that made no real contribution to the outcome of the war aren't my cup of tea, but they are interesting nonetheless in themselves. Enough said.
As for fastest twin regarless of engine type, I could not choose other than the Me 262. Though not a big fan of the type, it was impressive and showed the way forward for better jet fighters to come only a short time later.