An open world game needs content, a significant portion of which WILL end up as combat encounters. Being a Cainite, you are the predator, with Kine being the prey. Therefore to be meaningful in the slightest, the combat encounters ought to throw Hunters, Ghouls, other Cainites, Werewolves, and Magi at you. If these become common sight, it will start hurting my suspension of disbelief, and therefore it will start hurting the game (this is my main beef with VtMR, btw). The other solution is to level-scale the 3 hobo rapegang, which is just ridiculous.
So no, an open world game will not lend itself well to a Vampire game. The world will be either empty, or patently nonsensical.