Some wizards, tower wizards, necro-wizards, lonely wizards, have the time to commit to exceeding the typical human limitations of knowing the unknowable. As you approach the Planck scale of magical minutiae it passes beyond mere education and study, as this level you must cheat.
These cheaty boss-wizards should be freely given outrageous skill and stamina ratings. Huge, gigantic, suicidally dangerous sorcerous chops. The players can go ahead and literally brute force the issue of killing them, or they can be smart and figure out exactly how this bastard is cheating and catch them out.
When these weaknesses are exploited the wizard's skill and (total) stamina is halved. Some might just apply to the individuals exploiting it, or it might cause the wizard to be generally weakened. The exact details will suggest themselves.
D66 Wizard Weaknesses
11 - Having his hat knocked off. Its special lining was keeping the spells inside.
12 - The pet rat he keeps in his cummerbund, a great sorceror in its own right
13 - Seeing a tattoo of a bare bottom. Prude or ancient pact with Slaanesh?
14 - An albino ferret, brandished. The wizard cowers and cringes, obviously disgusted. Whether this effect is magical or psychological is unclear.
15 - The secondary brain they keep in a jar under their bed helps them think.
16 - A deck of cards full of occult symbolism. the wizard has actually invented a revolutionary note-taking system allowing him to offload a lot of the mental strain on to small cue cards. Regardless, destroying them would be quite a set back.
21 - Direct sunlight causes the warlock's crystallised plasmic crown to evaporate. It is otherwise invulnerable and irremovable.
22 - The daemonic parasite which clings to the back of his head. To the ignorant observer it looks like a rather gaudy evil-guy hat, but those viewing it via Second Sight will know differently. They must also test their luck or be blinded by the brilliance of the creatures true form. Daemonic hat - 5/20/4
23 - The true wizard is an old man behind a curtain in the room beyond, controlling this simulacrum with gossamer tendrils of plasma disappearing off into the ether. Requires a good few hours to rouse himself, so is essentially defenceless.
24 - Warlock wands are old fashioned, something a grandpa-wizard would use. A few enthusiasts see past the passe and into the pragmatic, creating extravagant wands of manticore spine and unicorn feather to compliment their abilities. They are tragically easy to break, however. When hitting the wizard successfully you may test your luck to break the wand. If you fail you do no damage to anything.
25 - One thing that never goes out of style are bangles and talismans. One of these doodads is the source of the warlock's power. Test your luck when grabbing at them to nick the right one.
26 - When the wizard says he has more power in his little finger than you have in your whole body, he is being entirely literal. Cut off that finger! Test your luck to hit the finger and deal at least 3 damage to it.
31 - Once a year at a particular juncture of the aeons the wizard goes out amongst the people and, into the ear of one poor fellow, mutters the word that will unravel his power. The person listening doesn't know what the word does, but they do know they will die in a year and a day if they ever reveal it. Anyone else saying it is fine, and greatly upsets the wizard.
32 - Every wizard worth his salt knows that copious consumption of fairy blood grants you elevated magical mind powers. However it also makes you very weak to the touch of cold iron and requires an industrial quantity of tiny faeries. Ecologically unsustainable.
33 - The wizard is careful to surround himself with mirrors at all times. While in the presence of a reflective surface he maintains his elevated state.
34 - Usually kept tucked up in his gums, the wizard chews on the psychoactive mushrooms that grow in dragon turds. Separated from his stash he will soon come down.
35 - The warlcok stole all his power from demons way above his station, but because of his high-heeled ostrich boots covering his tracks he's kept the demons off his tail. He's strapped in quite securely so they'll need cutting off, but when his feet touch the floor the demons will come and claim him. 1 in 6 chance the gate stays open.
36 - Standing in his foyer is what was once a flattering sculpture of the sorcerer but is now partially obscured by blue moss. As the sorceror taps into the false image of the sculpture it is further taken over by the 5th dimensional moss. After a few years of everyday use, or 6 months of intense wizarding, he will commission a fresh one.
41 - In an egg in a duck in a pond in an island in a lake in pocket dimension in a box in a cupboard is the source of (half) his power. The box must be found, entered, and hex-crawled.
42 - The warlock has sacrificed his mirror-self for power. While held in a full body reflective surface his powers are diminished as the astral corpse of his other self retakes its position.
43 - Their claim to knowledge is so great that if they were to be presented a riddle that they could not answer their confidence would be shattered. Will always answer riddles. The group may collectively offer one per round and if the GM can answer it the wizard is assumed to have done so. The GM may also roll the wizard's luck once to solve it instead.
44 - The wizard isn't bad, he's mad; subtle senility has settled over his already power addled mind. Anyone researching and performing an adequate impersonation of his wayward son will rattle him profoundly.
45 - The wizard has replaced all his blood with liquid magic. He needs to put it back inside once in a while, and without it will be terribly weakened.
46 - All of his organs have been put into (2d6) jars and hidden in secret places. Each one foudn and destroyed takes a portion of his power.
51 - The wizard sits in the middle of a miasma of chemical unguents with the distinct tang of body odour. However, he is not just a disgusting human being too wrapped up in the pursuit of power to wash, he is actually cultivating a vast colony of bacteria and other ambulatory filth to offset some of his sorcerous strain. A good amount of soap and water should put an end to his reign of terror.
52 - Light is a terrible trickster, if one could avoid the sloppy interaction of radiation and surfaces and get down the the nitty gritty objective reality of things we would all be wizards. Now imagine if someone who was already a wizard got that insight. The wizard is blind and manouvres around his manse with a series of seeing stones mounted in ceiling orbs and hidden on bookshelves. Inside his house his is powerful and omniscient. Outside he carries a small bag of variously sized stones for on-the-go observation of the objective world.
53 - Being fully undead has many many problems. Minor injuries become permanent problems, the smell is awful, your joints get all gunked up, and so on. Why not just have an undead heart? While it still beats in his chest he is immensely robust. Somehow he can function without it. I don't know how.
54 - The wizard cannibalised a wily demon and took his hands and tongue. Allergic to religion
55 - Every night the sorceror sleeps in crystal pod which guides his dreams and reverses the rigours of age. Without access to it he will lose its calming powers and become tired, old and cranky.
56 - Bit by bit the warlock has replaced his bits and bobs with mechanical parts. His blood is creamy, plasmically charged goo, his hands weave spells without a thought and he's got sub-dermal weapons under his synthetic skin.
61 - The warlock maintains many many clones of himself. d6 are currently active while the others are in their rest cycles in vats of goo. If you can find and smash the original to bits they will loose their hub and focus.
62 - The wizard doesn't have a weakness, he's just really great. He will however act like he does, begging them not to touch his special deck of cards or say bad words. He finds it funny.
63 - The unimaginative magic worker sold his soul. If you tear up the contract it's void.
64 - In his basement he keeps a fairy/genie/angel or other adorable but magically potent creature rigged up to a transmitter tower and feeds of it abiently.
65 - The wizard has an agreement with a dark(er) lord to boost his powers
66 - The wizard delegates much of the physical toil of magic to his apprentices, who remain mind-linked throughout the apprenticeship. Any stress of hardships befall them instead of the wizard. Most don't last long.
A lot of these seem like the kinds of things that would be incredibly impractical limitations in combat. Remember they are wizards, not soldiers. Their magic is to further their inscrutable ends, not arm wrestle (unless they're endomancers I suppose).
(This is written for Troika, which is freely available)