The Foundations each represent one cool thing mad scientists do, and one reason sane people fear mad scientists. The Artificers for example are the guys who build awesome stuff and the people who force everyone else to adapt to new technology. Whether they like it or not.
The Baramins each represent one common way intellectual thought goes horribly wrong. The Atomists for example are people who try and force technological solutions to social or political issues.
Complete Monster: Walking-Man, Peripatetic Dreamkiller, is the most infamous of the Clockstoppers, and one of the most powerful. Targeting small, isolated communities, Walking-Man uses his Compelling Voice to take control of the town, has mobs eliminate anyone who might object, and then disposes of the town's leaders, taking on that role himself. Forcing people to abandon their modern conveniences, Walking-Man drives the communities he rules farther and farther back in time, finally sending them into the wilderness, unclothed and unarmed, to die, while he searches for his next target. Having thus caused the deaths of communities in Idaho, Nebraska, and Colorado, Walking-Man continues to ply his trade across all three states, preaching his anti-technology gospel to any who are susceptible—although his relationship with Lemuria would indicate his hatred of technology does not go as deep as he might pretend.
Crazy Is Cool: Any awesomeness in the setting will likely be crazy by default. That goes for events as well as characters. Just to illustrate, this is a game allowing you to play Mad Scientists who can bend the law of physics through their madness, visit an underground world populated with dinosaurs, time travel, and fight things such as Martians, Nazi Mad Scientists and Lizard Folk who may have formed a Reptilian Conspiracy.
Fridge Horror: The stock Ophidian Infiltrator has a larval Epikrato... egg. Ophidians are Snake People. Who most certainly reproduce by oviposition. Which implies it was an Ophidian egg. The mind control is then literallyPowered by a Forsaken Child.
Genius Bonus: Appropriately enough, there are plenty of references to be enjoyed by science and history buffs alike.
Jerkass Woobie: A number of antagonists. Lemuria is full of Geniuses who were simply snapped up before they learned what Mania really is, and former Peers who just couldn't live with knowing they're crazy anymore.
Special mention goes to Seattle's Argentine St. Croix, who, extramarital affair and killing her Stalker with a Crush aside, lived a relatively blameless life prior to her Breakthrough, and never wanted anything to do with Inspiration in the first place. Oh, and one of her sons is in a coma that even mad science can't fix. The other one publicly disowned her in a fashion cruel enough to shock some of his new allies.
Even Clockstoppers are sort of pitiable. It's not their fault they're spite-fueled avatars of ignorance. Probably.
The constant drum-beating on how expensive mad science is makes reading the book kind of a chore. Imagine playing with a Storyteller who insists on holding to that. In game mechanics terms, either you dump Merit points into Resources/Dumpster Diver or get a penalty to build any sort of Wonder - and unlike other WOD games, you're required to state where those Resources come from, practically begging the Storyteller to take them away from you.
The "Core Modifier". The better and more powerful a Wonder is, the higher the penalty assigned to all dice rolls involving it (the saving grace is that the penalty caps at -3). The only way to mitigate that penalty is to load the Wonder down with flaws and drawbacks. Worse, many Axioms use the Core Modifier as a basis for how powerful their effects can be, meaning you're forced to make your Wonders worse to make them usable.
They Copied It, So It Sucks!: Downplayed, as the game still is pretty popular, but there are some fans who accuse Genius of just having taken Technocracy leftovers from Mage: The Ascension and patched them together into a new game.
The Woobie: Three out of five Catalysts (Grimm, Neid, Klagen) are likely to involve a personal tragedy. In addition, all Catalyzations are generally traumatic; a person who becomes a Genius is a person who has been driven insane. It's probable that there are many, many Inspired Woobies.
Katastrofi: Doomsday devices; the rulebook's sample 5-dot weapon is a cannon that can demolish whole city blocks at a time, described as "some silly thing a Genius might make while trying to take over the world again".
Metaptropi: Permanent invisibility to the 5 mundane senses and magical detection for only 6 bound mania.
Invisibility to taste is probably unnecessary. Although... Ophidians are Snake People and snakes 'taste' the air to sense things...
But the fact that Prostasia can provide insulation against Havoc at any level makes it endlessly useful. Gotta love form-fitting force fields.
It's also worth noting that maxed out Genius armor gives a default Defense of 7, compared to a mundane bulletproof vest's Defense of 2. And it can go higher.
Prostasia as of its improved rules: Nigh-invincible fortresses. You say your orbital doom cannon just delivered 50 successes' worth of damage to my lair? Awesome! You'll need 150 more in that single attack to scratch my paint job.
There is also the Apokalypsi 2 universal translator which gives translator microbes to everyone in range. You can make a universal translator the size of a CPU tower that has a range large enough to cover the earth. While it doesn't give you godmode it would make a HUGE impact on the setting and completely mess with the masquerade. A starting character can build this.
If you combine Assembly Line 5 with any of the above, well... God Mode.
A theoretical Game-Breaker within the setting itself is the Axiom Apekrina, AKA Pankosmoi, AKA the Needle Grail. If it's real, this Axiom could prevent Havoc, enhance Inspiration, and even generate/harvest Mania from reality itself...somehow. There is no evidence that Apekrina actually exists, but mastering it would be tantamount to achieving godhood.
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