The quest for the One True System is important in its own right, I think. Without it, how to we home in on what exactly our tastes are, and what we want system to do? Certainly it's been an important component of my own roleplaying "career", and I say this even as a guy who generally doesn't really care about system very much, and am not in the least a system junkie. I do find, however, that I want a broad system that I like well enough that I can use it in a variety of formats, for a variety of games, and a variety of genres without much tinkering to get it to work there. And as I've homed in on systems that I've liked, I've tinkered a lot with aspects of them.
For years, I looked at d20 Modern as my One True System; the last system I'd ever need. Even for fantasy, I'd take the d20 Past book, and the Shadow Stalkers campaign model, and use that (in lieu of D&D, for instance) because it better matched my taste.
Over time, I've become less patient with the complexity and clunkiness of the system, which I had previously thought I'd made peace with, so I'm starting to migrate a bit into m20 territory. But since m20 is a derivative of d20, I don't see that so much as a change in systems as it is a refinement and honing of the system to be a bit better adapted to my tastes than it already was.
I do miss a lot of the character definition options of a more fully robust d20 variant, but otherwise, I find that m20 (Modern) meets my needs ideally.
As others have said, finding a One True System doesn't mean every detail of the system, though. In order for it to be One True System, it needs to be flexible, modular, or adaptable enough to be used in a variety of genres, and with a variety of tones and feels. Depending on how strict you are about defining a system, there is, of course, no such thing. If you take a looser approach, though, you can have a family of very closely related, yet slightly different systems, that work for almost anything you'd care to play with the exception of extremely divergent ideas. I think that's not only doable, but even desireable for most gamers.
But again, I don't assume that most gamers are system junkies who enjoy playing games specifically because of system. What most gamers (IMO) want is to play without the system getting in the way.