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I'd like to start by saying I 100% support Permadeath especially with this IP. As a long time player of White Wolf products I can say it's 100% necessary.
That being said it's very difficult to inflict the True Death in Vampire: The Masquerade. It's not something you'll see very often I imagine and would require considerable effort on the part of the aggressor. Also, it's illegal within Camarilla territory. Any Kindred caught violating that particular rule would face a blood hunt and quite possibly the True Death themselves.
Basically the options for permanently killing one of the Kindred is Aggrivated Damage, Decapitation, Massive physical trauma, and Diablerie.
Aggrivated Damage is essentially supernatural damage. It bypasses supernatural creatures normal defenses and renders them essentially mortal. This kind of damage usually comes in the form of varius disciplines (Vampire magic!) like Feral Claws from Protean, varius Tremere spells and a few others. Fire also works, but any Kindred using fire usually faces Rotschreck which is an involuntary fear response all Vampires have when faced with fire. Finally, Garou are bad. It's unlikely we'll see Garou when the game first goes live.. but.. yeah.. Even the youngest Werewolf is a combat monster with easy access to Aggrivated damage (Their claws and bite), regeneration, and a 10 foot tall Crinos form (I WANT TO BE GAROU!).
Decapitation is exactly what it sounds like. Cutting off a Kindred's head does the job nicely. This is the primary reason most Elders disdain guns. Although a high enough calibre round to the melon does the job just as well as a finely honed blade.
Massive physical trauma is basically anything not covered above. Kindred are very durable and heal incredibly fast thanks to vitae. Still, throw enough bullets at them and they will die. It just takes A LOT of bullets.
Finally we have Diablerie. It essentially means one Kindred consuming another. It's quite possibly the most heinous crime imaginable in WoD, at least from Camarilla point of view, and it leaves detectable black marks on your aura. So yeah.. hard to get away with.
I am all for Perma-Death in the context of the WoD. I would bet on it being very rare and you would have had to take a very unsuccessful run at the Princedom and be a pretty huge thorn in the side of your city's Kindred society for a Blood Hunt to be validated. (building some kind of strike tally against your name that may require time, blood or favours to redeem)
As far as I gathered from videos and tid bits the Masquerade being broken may actually be a really hard thing to do. I'd guess we'll be jumping between Havens and Elysium social spots so breaking the traditions at all will essentially be impossible (and good, because frankly the less mature and more volatile players would certainly test the bounds constantly).
I am not worried about Perma-Death from PVE combat, it is just not going to happen. Would be interesting if Torpor is required to get over some injuries though.