Everything I have ever tried has made a difference of some sort.
Whether or not I cared for the difference is a different story.
Let's never underestimate those two above observations for two below reasons:
1) If we make a single change to our systems, even if it is not audible at this moment, our next upgrade (such as a new speaker or even a more minor component), might be differently affected by that exact change now. In short, an audio path is a chain of mutually-interactive components where each emphasizes the inate problems or advantages of all each other components (in a specific listening room!) and is in reality never guaranteed to have the same absolute result totally independent from all other components.
2) Throwing big money on our audio setup may often be equivalent to being able to buy a supercar, but not having the proper training/experience/objectivity to "drive" it. After all, audio paths are too often maintained on the basis of bigger-must-be-better, which can be simply "attested" by their ticket price. The real audio value, however, is not determined by words and numbers, but by our never-objective ears. Sadly and quite easily, we may end up like drivers in those Youtube videos of idiots damaging their supercars. Objectively, the above comparison is quite accurate: there are plenty of people out there with great means who lack ear training and sufficient hearing ability to pursue optimal component matching.
That's why audio forums are important and useful exchanges of subjective facts and must resist the dangers of creating and maintaining "audio absolutism" cults.