The question is: would it work for you for the story to shift in scale from "investigation into odd rash of murders and disappearances and so on" to "fate of the world at stake", and if so, how much of the book would feel reasonable to you to devote to the initial investigation without it feeling like a cheat or a disappointment for it to then become something that different ?
Yes. The shift works. Love it, in fact. (Have a similar escalation in the draft I just finished.) I've seen this kind of shift plenty of times in books and movies. Just off the top of my head, Indianna Jones and the Last Crusade, Dresden Books 4 and 7, Angels and Demons.
all use a similar shift from localized trouble to something that could impact the fate of the world. So, no worries there.
As for how much time to dedicate to the different aspects of your story—I think it just depends on your pacing, character arc, etc. You'd mentioned that the story you envisioned is much more about the game-changer than the assassinations and whatnot. If that's the case, I'd recommend moving it along briskly to the point where the story becomes about the competition for this artifact. (It seems like this artifact serves as a type of McGuffin, correct?)
I recommend checking out Dan Wells' presentation on story structure if you get the chance. (It's on youtube.) He discusses an approach to writing that involves using two "pinches." Each "pinch" is a major turning point in the story. He defines the first pinch as the point of the story where the characters realize that they're dealing with more than what they bargained for at the story's outset. This sounds like it might be relevant to your question, so you may want to check it out and see if you can apply any of it to your WIP.