In a Pre-3e, Non-AD&D Campaign, I invented my own form of "Pseudo-Immortality" power. It did grant regeneration, but in each case, the PCs had an unknown Achilles Heel. When they acquired this power, they had it at "Skill Level 0", and could raise it to level 10. Autoregeneration was a task, requiring a roll. I also had them roll 1D10 on a table to determine how their Pseudo-Immortality could be defeated...
1) Piercing the Medula Oblongata (base of the skull).
2) Piercing the Pituitary Gland (middle of the forehead).
3) Beheading (Neck, with a slashing weapon).
4) Psychic attacks.
5) Piercing the Heart (Chest).
6) Removal of a specific organ (As specified).
7) Drowning.
8) Burning.
9) Suffocation.
10) Something even more unusual
Some of the original material (Copyright SteveC 1998-2003. All rights reserved) is included, below:
Pseudo-Immortality
Description: Pseudo-Immortality (unless killed, the Psionic will live forever, and even killing them is tougher)! This psionic science includes improved versions of Autoregeneration and Immunity to Age, and increases the Pseudo-Immortal's chances of curing themself of both poisons and diseases.
Range: Self, only.
Area of Effect: Self, only.
Duration: Constant.
Acquisition: Requires finding a teacher, being trained by them, a high Psychological Strength, one or more other *** capabilities, and a lot of luck. If you want a Highlander-style campaign, this is a fun one to spring on your PCs unaware, only informing them of it when it saves their life. The Referee can assume that a few individuals every millenium or so have this as a naturally occurring ability.
For game balance, Pseudo-Immortality confers no protection against some other form of less traditional slaying (although the Referee need not reveal this to the Psionic PC's player). Pseudo-Immortals slain in this fashion are permanently dead, regardless of their abilities of Autoregeneration. The Referee can choose an appropriate type for NPCs or critters, or have the PC roll 1D10 to determine the type of damage that ignores the Pseudo-Immortality: 1 = Piercing of the Medula Oblongata (base of the scull), 2 = Piercing of the Pituitary Gland (middle front of the head), 3 = Beheading (neck), 4 = Psychic Weaponry and psionic attacks (anywhere), 5 = Piercing of the Heart (Chest), 6 = Removal of a Specific Organ (As specified), 7 = Drowning, 8 = Burning, 9 = Suffocation, 10 = Other (In some rare cases, the Referee may want to make the PC who rolls a 10 vulnerable to something really unusual, besides weapons; pure or salt water ("I'm melting!"), pollution, smog, garlic (or some unearthly, local weed, probably from the Pseudo-Immoortal's world of origin), etc. Use your imagination.
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You will no doubt notice that I drew heavily from myth, legend, and modern TV to make this chart! #1 comes from the X-Files ETs. #2 I created, based on Psi fiction. #3 is obviously from The Highlander. #4 is, again, Psychic. #5 is from Brahm Stoker. #6 from many a legend. #7 is the opposite of #8, which is how the Trolls die. #9 (like 7) is another way to die, and #10 explains the remainder of the Vampire legends (they have a very poor form of Pseudo-Immortality)!
Naturally, other ways to die, permanently, include starvation, poison, disease, caustics, electricity, cold, level draining, etc., etc., ad nauseum. I'm sure you can extend the chart to 20 types, if you prefer...
Once you know what will kill the PC, keep it secret from them! ;-P
This can also produce some interesting effects, such as when I generated an aquatic creature who could only be permanently slain by Drowning! (Basically, this lucky critter WAS Immortal!)
One thing I had that 3.xe doesn't, though, was a method for determining where a blow struck... Otherwise, you will have to create a "Called Shot" rule, to determine if the MO or PG, Heart, etc., gets hit...