
Disease as plot: Diseases have one useful feature when it comes to driving plots. They have a built-in countdown. A PC might have a certain time to get the cure before he dies (or is permanently maimed or brain damaged, etc.), which can drive the plot at a breakneck pace. Conversely, a 24-hour virus might put the character at a disadvantage at the worse possible time, but can be waited out, allowing her to bust out the fists of fury in the endgame.
Disease as risk: In one-shots or games where death is expected to occur and survival is its own reward, players may be tempted to excessively armor their characters. Ok, but does that armor protect them from illness? Even a face plate can crack.
Disease as nerf: Non-lethal diseases can be used to reduce the effectiveness of PCs as an added obstacle. A simple cold might impair a character's attribute and skill challenges (seduction with a runny nose, or strain on one's Constitution), but in worlds where special powers are possible, illnesses that affect those powers are also imaginable. How does a particular disease affect spell-casting? What about super-powers? And could some viruses only affect those that make use of such powers?
Suggestions

Magic games: Magical diseases could produce any number of effects. Imagine a contagious curse. Or a disease transmitted through spell-casting (an MTD). Maybe some creatures in your game world are simply people suffering from a plague. What if zombies aren't really dead, for example? Lycanthropy and vampirism are certainly communicable.
High tech games: Robots and cyborgs have to deal with computer viruses. Or how about nanites that eat at their metal implants? And if Star Trek is any indication, diseases could cover psionic parasites, temporally out-of-phase viruses, and conditions that mutate your genome or make you aphasic. There's no real limit. It doesn't all have to be radiation sickness.
Now go out into the world and sicken your players! And if you'd like to play the game like Pout did, feel free to suggest topics in the Comments section. I'll add them to the hat.
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