Theme Hospital/YMMV


 * Demonic Spiders: Epidemics (contagious diseases that have to be vaccinated and cured within a time limit) have a habit of both wrecking you when you're down, and snatching victory away from you when you're just about to win.
 * Combined with Unwinnable By Mistake, as Epidemics are so annoying because of a particular bug: The idea is that you need to cure all the disease-carriers before they leave the hospital. Unfortunately, "leaving the hospital" includes "walking out any door", and in most levels your wings are arranged in a way that travel between them requires going briefly outside. Unless you block most of the exits (with potentially terrible consequences for pathfinding, not to mention hospital efficiency) and make sure outlying buildings are never used for diagnosis or treatment (which can be impossible on some maps), prepare to get hit with thousands of dollars in fines every few months...
 * Fridge Horror: Curing Bloated Head, or slack tongue: You get your tongue sliced off, or your head popped, and you pay for this whack-o treatment. Are these even real doctors?
 * Goddamned Bats: Diseases that can't be diagnosed in the "standard" diagnosis rooms (General Diagnosis, Ward, Psychiatry), requiring you to research and buy more advanced diagnosis equipment. Ironically, the more visually obvious the disease, the harder it seems to be to diagnose (Invisibility and Slack Tongue require the X-Ray, Transparency and King Complex the Scanner). One way to combat this is to put your best possible doctors in the GP's office, so they can diagnose as many patients as possible without requiring extra equipment.
 * Surgery patients - surgery requires a ward, an operating theatre and two surgeons (sometimes it can be hard enough to hire one).
 * Most Annoying Sound: "Two surgeons required in Operating Theatre!"