I was mulling over a game that would occur at the Conjunction of the Spheres...or just after it. Playing as a group of regular, desperate people who decide to hunt down some monster terrorizing their land. During the course of the prologue, you play as each of these characters in turn. Each of them makes some sort of profound discovery about what these "monsters" are and where they come from before being killed off (in gruesome fashion, of course) by one beastie or another. Upon all of the other members of the party members being killed, the perspective shifts to the final character, and you somehow come into contact with the first mutagen. (I've debated it being something like a spore or monster venom that the character accidentally ingests, a potion or brew given to the player by a monster like a godling, or even a "hunter" from some other plane of existence that purposefully forces the character to take it...but frankly, I don't like any of those ideas much.) The only thing I think should be clear is that taking the mutagen is an intensely bad idea, but the character has no choice.
Following that, and since mutagens prolong life and health, I'd have the story skip forward, say, 50 years, leaving much of that time steeped in mystery. The character from the prologue now meets the player character and s/he gets wound up in "hunting monsters". The course of the game would be discovering the source of new mutagens and basically experimenting on yourself or other characters that team up with you (not always successfully). The knowledge of how the character from the prologue knows these things (the missing 50 years), would provide a source of dramatic action and discovery to further the story and introduce how the witchers came to be.
Major mechanics would be mixing mutagens to unknown results. Perfect combinations would give only a significantly positive result. Getting close would result in a permanent, moderate improvement and a temporary debilitation. Failing big-time would grant a significant ability and a significant debilitation -- both of which are permanent. (Hence, the player may choose to test things on other characters first, creating a skin-crawling take on "teamwork" and generating some interesting character dynamics.)
Combat would be about learning to take advantage of the abilities granted by the mutagens, and developing moves and combos that would differ based on whether the character mutated to become faster, more agile, stronger, more precise, etc.
Monster hunting would be less about finding books and lore on monsters (since none exist), and all about actually investigating for clues, observing them, and invariably, learning things the hard way.
The end of the game would be the player character becoming the first ever person to be recognized as a "witcher".
(However, this is taking enormous advantage of the license. I would want to ensure that what was created was as close to the canon of Sapkowski's world as possible.)
