I used to play the old Chaosium rules, 2nd or 3rd edition I think. Still have the rulebooks tucked away somewhere.
The two best usages I've seen of it:
1. Indiana Jones meets AAAAAUGHWTFISTHAT?!??. The investigators are pulpy heroes (the swashbuckling archaeologist, the millionaire secret Golden Age hero, the hardboiled gumshoe, etc.). Throw in plenty of Nazis and Nazi occultism and then slowly tie in the Mythos. Bear in mind that most of your players will be genre-savvy, so fuck all that up by never letting them know exactly what it is that's out there. By coming up with new things that they never saw in a Lovecraft story, but which fit the genre. Hell, one of the most terrifying encounters we ever had in a game like that was an escaped Nazi Ubermensch clone thing in a U-boat. Basically, running from bow to stern through the compartments, shooting at it and trying to lock the compartment doors to buy enough time to get to the rear hatch, then setting off a flare gun in the diesel tank as we all jump off, Hollywood style.
2. Alternate horror genres. Chaosium actually published a pair of scenario books based on different classic horror tropes (vampires, werewolves, demonic toys, possessed children, theatrical serial killers, etc.) and using the CoC rules. FUN STUFF. Especially the second book where they dug deeper and you had a scenario where your characters were luchadores, echoing classics like El Santo vs. The Vampire Women. If you have a group that are film buffs/horror buffs/incredibly genre-savvy, this can be a riot.