These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Darkness-Induced Audience Apathy: See main entry for details. Brief recap: the 3e and early 4e sig characters were largely antiheroes. The current 4e sig characters are rapists, vivisectionists, spree killers (who in 3e were specifically held up as examples of bad shadowrunning), and amoral assassins. Oh, and FastJack, grand old dean of shadowrunning, is now starting to go senile, though this turned out to be a red herring...
Game Breaker/Elite Tweak: Third Edition has an Edge called "Connected" that, when taken for a vendor contact, allows you to buy from that contact at the list price or sell at the street price, which can be as much as three times more. Thus, taking that edge for two contacts (one to buy from, one to sell to) allows a player to get ridiculous amounts of money while the GM isn't paying attention.
The physical adept can become noticably broken if you use initiation to offset the Essence cost of cyberware.
The chemical DMSO. If you splash it on someone, it allows for other chemicals to be absorbed into the DMSO-coated skin. Additionally, armor has little to no effect, so if someone hits you you with it, you WILL be affected. The end result being that if you mix DMSO with poisonous drugs and load it into a squirt gun, you get a super soaker that deals one-hit kills. You can hear details about how this can affect a game environment in this video.
In the Genesis game, there's a shop you can sell stolen data to. This is easily the most profitable activity in the entire game, enabling you to quickly upgrade your deck to steal larger and more valuable files, in addition to making it trivially easy to obtain all the best equipment. To give an example of just how broken it is, a single-run on a high-end system will with near-certainly net you three times more cash than a shadowrun from even the most well-paying client, and that's at a minimum. A single file from the big corporations can be worth three times as much as a single shadowrun, sometimes even more. You can even do it in tandem with a hacking shadowrun to get the karma payout in addition to the money.
Cyberzombies, which are metahumans implanted with so much cybernetics that they effectively die. Their souls are then forcefully tethered to their bodies through magic and technology. Few last longer than a year before cancer and necrosis rots their bodies away, and most of them aren't what you'd call sane. Oh, and all of this is done completely against their wills by corps who want a temporary asset.
Chicago, which ended up suffering an outbreak of nasty insect spirits. Much of the city was blown to hell trying to get rid of them, and what remained was quarantined by the UCAS military, leaving everyone still there to fend for themselves. And that was the good ending of this saga.
They Just Didn't Care: prebuilt characters from the 4th Edition corebook. There is something wrong with every one of them. Barely any have a Fake SIN (basically an ID card required in all civilized areas), and that's just the beginning. The Technomancer? Gets -1 dice to Reaction and Agility tests because of being encumbered by worn armor (the "maximum armor" rule is stated in the same book, no less). Same goes for the Weapons Specialist from the More Dakka entry. She also doesn't have anything that would allow her to use that laundry list of guns more than once per turn (as opposed to other combat-oriented premades like the Street Samurai and the Gunslinger Adept). Drone Rigger? Has cybernetic eyes (with Image Link modification built in by default) and goggles with Image Link as the only modification. Even with no Min-Maxing, a player with experience in Point Build Systems would achieve better results.