Hmm, I'll be reading through that site for a while I think.
Having seen some fine pimpin', I think I'll take a crack

. First, having kicked around the idea myself for a home campaign, I came up with two elements that can very quickly keep immortals in check vs. mortal PCs.
Reverie & Signature
Immortals apparently retain most of their memeories, and activity the human gray matter just isn't designed for. We're constantly seeing the principle characters go off into flash backs. I though it would be an easy tool to control them if they don't have any control over this mental behavior. They just black out some times (stuck in a flashback in their inner mental landscape), and the older they get, the more it happens.
Immortals can sense each other. What if (and this is pretty easy to justify) the degree to which an immortals presence makes itself known to the others is related to how many times they've killed other immortals? Now you have a nice, self-balancing counter on the character sheet. You have to kill X number of other immortals as a prerequisite to gains certain feats (growing quickening powers...) or as an entry requirement for an immortal only prestige class (think the Kurgan, only gaining lots of physical power for following his dark road of slaughter). These characters are easier to sense. Hell, everyone knew when the Kurgan was on the same continent practically

. While some of the truely ancient were almost undetectable. Obviously extra sensitivity to Signature, and extra ability to mask it have potential for feats.
Mechanically, I'd use Spycraft (naturally

), and say that immortals convert all damage except melee weapons to subdual damage. Getting shot a lot can drop them, but thats about it. Getting stabbed (even in the gut) really seemed to get their attention. This is a nice, juicy advantage, but it's hardly game breaking. An irate immortal could have annother gunned down (rendered unconcious by riddling the body with lead) and then decapitate the victim at his leasure. Coup-de-grace actions with a blade are still lethal. Add some immunities to drowning, and you're pretty much set. The immortal gets this in place of a normal agent's department bonuses. This in not a bad trade- the imortal gets some damn good abilites up front, but also the ever present threat of being head hunted by someone more powerfull, instead of the fairly butch bonuses granted to a super spy. Might do a Watcher's Department just for fun

.
You might create a new base class for older immortals (with lots of skill points!), but with Spycraft normally providing for superspy level competence, an Immortals class would be pretty bad a$$, and your mortal PCs are not going to be standing around looking useless

. Add a new quickening feat tree for their diverse talents, crack open the Modern Arms Guide for exotic weapons and the Pan Asian chamberbook for 40 more melee combat feats, and you're ready to go.