Hard to argue against the 109, it sure was a brilliant design considering it lasted from before the war until after it, or at the very least it was the most improvable design of the war. Galland said that it was in his opinion the best accelerating fighter in nearly every stage of warfare throughout the years, and that acceleration was one of the most important features to him in terms of combat. Very subjective discussion, and I agree that depending on the mission and purpose, the answer could be argued to be a wide variety of platforms.
I do think that the last two years produced fighters that would have absolutely demolished anything from the previous years. Imagine the BoB with Fw190Ds or 109Ks, and so on. In just a few short years the capability of the front line fighters increased at a rate we'll never see again, in all metrics, be it speed, armament, range, ease of use.
One thing that's always stuck with me was Osprey's book on the 190s, and accounts in it from most of the pilots who switched to the 190 from the 109 and other fighters said it was like jumping forward in time, and I can understand that based on their descriptions of the very advanced features it had making the fighter pilot's job easier. In terms of the most modernized fighter, IMO the 190 could probably take it.
Strong case for the Mustang as well, regardless of whatever numerical advantages it had, it's mission was harder than the defenders by definition IMO - having to fly a long way into enemy territory and wrestle air superiority from a foe over his own territory is no easy task, and it was the first fighter in history to really do it.