Without wanting to sound like I'm kissing ass, the quality of CDPR's games, their talent for story telling and their world building mean that most of us here can easily get excited about them making pretty much any RPG-heavy game. Yeah, a VtM game would be an amazing prospect.
Middle-earth, Star Wars, Mega-city 1, Forgotten Realms, Planescape, Escape from New York, Shadowrun, Werewolf, Mass Effect (hehe), Hyboria, some kind of steampunk, - whatever somebody's favourite settings are, having CDPR make it would be exciting and probably take it to a new level.
But, sadly, they can't make everything.....so I'm guessing they'll stick to stuff no one else has done before on the big stage. It avoids comparisons and has more chance of feeling fresh. Not to mention the problems of licensing etc...
With that in mind I'm really hoping they announce the other AAA game supposedly coming before 2021 at E3, at least enough to know the genre, sci-fi, fantasy etc,. I wonder whether it'll be an established fictional world they've got the license for or their own creation?