What is the saddest transmission, symptom, or ability?
I would pick extreme zoonosis. Extreme zoonosis is probably the best transmission, rawly speaking, but it is outclassed by air and water because you need to get to islands. Also, it is extremely expensive. Not expensive enough to be a problem, but expensive enough to lock you out of buying other good stuff like air, water, cold and drug resistance, etc.
Vampiric thirst or whatever is it called is also sad. With Necroa Virus, you are stuck evolving the right side of the symptom tree so that Z com does not curb stomp 50 million zombies you wasted like 18 DNA points sending at them. Vampiric thirst and whatever that other symptom was are symptoms that function the same as dopamine inhibitor: less consumed people die, more become zombies. Air 3 on Necroa Virus is also sad because by the time you get Cytopathic Reanimation, you are halfway cured.
Weapon creation on Simian Flu is also sad. You can get away with using just rampage on cure facilities. If you get it, you can destroy a facility in one day, but it does not make a difference enough to justify putting DNA points into anymore than putting it in seafaring and logistics.