One of the most curious bits of random Yog-Sothothery was in the d20 Call of Cthulhu book. In the appendixes, Monte Cook (or whichever of the writers wrote this section, but I'm pretty confident in that call that it was him) talks about doing the obvious--importing Cthulhu and other Mythos monsters directly into D&D, because after all, any iteration of the d20 system back then was still sufficiently similar to any other iteration that it was really easy to do so. There was a bit of Wayne Reynolds artwork of the early 3e iconics getting trounced by a little Cthulhu cub or something. This bit of art has become quite popular amongst gamers, and I've seen it reposted numerous times over the years since.
However, I think a lot of gamers just really don't understand Lovecraft, to be honest with you. In the most recent posting of it, someone posted that picture and the question: have you ever had a team of high level characters fight Cthulhu, and if so, what was the experience like? One guy responded immediately that if the players won, then something was certainly wrong the system used to run that combat. And then a moderator on the site, one who's usually fairly intelligent, and who usually posts from a position of knowing what he's talking about, added to that that maybe there's nothing wrong with the system, but it clearly didn't match Lovecraft's writing.
This was not unique to Lovecraft's writing. A posse of federal agents put a decisive end to the lair of the Deep Ones in Shadow Over Innsmouth. A handful of old professers with access to a banishment ritual of some kind put a decisive end to the monstrous "half-brother" of Wilbur Whateley in The Dunwich Horror. Randolph Carter flouted the designs of no less a villainous team-up than Nyarlathotep and Azathoth simply by waking up in The DreamQuest of Unknown Kadath (although, sure, I'll concede that he didn't kill them in mortal combat, exactly.)
Who says that defeat of the Cosmic Horror is not in line with Lovecraft's writings? This leads to some of the same inane problems that Cthulhu games inevitably have--unskilled or inexperienced Keepers (or whatever they call Cthulhu GMs) think that if they're not chewing through characters 2-3 or more per session, then they're somehow doing it wrong. This means that, in my experience, Cthulhu is often viewed as a campy one-shot or convention type game, completely unsuitable for campaign style play. What a sad state of affairs! Cthulhu can and should provide some of the best campaigns you can get. But not if the GM and players don't really "get it." And part of "getting it" is 1) actually understanding Lovecraft's writings, and not going on a half-baked, second hand interpretation of them, and 2) recognizing the nature of Yog-Sothothery and what it is supposed to be. Heck, Lovecraft himself expected that his Yog-Sothothery circle would do different things with the themes and memes of the Mythos. Robert E. Howard wrote all kinds of Mythos stories in which the Mythos was rather heroically handed its rear end by a two-fisted, gung-ho type guy (like Solomon Kane, for instance.) And Lovecraft thoroughly approved.
The idea that Lovecraft wrote only about shy, retiring characters who were doomed to failure is not supported by "the primary sources." It's really an artifact of what's come after--long after, in many cases--Lovecraft himself had died.