Issue #2: I'm Sick of This!
Ah, sickness. Aside from children, who get out school, and people who hate their job, who get a day away without having to "kill" their fourth grandmother this year, I doubt anybody likes being sick. You feel bad, usually you try to not see other people, and often you have unfortunate substances of various colors and viscosity leaking, oozing, or otherwise escaping your person. Sometimes violently. Ugh.
On the flip side, even if you weren't trying actively to avoid people, chances are pretty good that people are shunning you like you have the plague. Which you might. People on the bus move away from you, co-workers all but beg you to go home; basically you are treated as a pariah; unclean and outcast.
Where the hell am I going with this? Good question ... oh, right. Disease and sickness. In your games. In your player characters.
Being sick isn't something that everybody can "afford". Plenty of people have a livelihood riding on their daily work, if they are sick they have to "man up" and work through it. I doubt a farmer, a real, legit, hands in the dirt farmer one would see in a fantasy campaign is going to take a day off unless he's all but falling down, or if his wife tells him to rest. The same applies in fantasy games to all lines of work. Almost all; one expects the village healer to at least not be coughing up blood, if not outright healthy, he is the healer after all. Still, if you need want to infect your PCs with an illness look no further than, well .... just about anywhere. The barmaid, the weapon smith, the local alchemist who buys those girdles of masculinity/femininity off of the heroes cheap and then sells them at enormous markup to those kinky transvestite elves in the next forest over...
... woah, sorry about that, my rhino-virus addled brain got away from me ...
OK, so why make your characters sick? Well, you could do it as part of a larger game plot. Perhaps they really pissed off the wrong God. Or maybe they shouldn't have opened that long sealed tomb/facility/space pod. Maybe it's the end of times, the seals are being opens and the PCs, in their infinite stupidity, have decided to go mano-a-mano with Pestilence Himself.
Or maybe you want to be a dick. Admit it, when you act as the Storyteller/Gamemaster you sometimes just enjoy being a douche. It's a perk of the job.
Remember last session when one of your players laughed about how easy it was to clean out the Kobold caves and retrieve the MacGuffin of the week? They won't be laughing when they come down with the same debilitating illness that laid the Kobolds low. Then again maybe the opposite is true. A player with a racial hatred for Orcs comments on how Orcs never really pose a challenge because the group is much higher level than they were a dozen sessions (or more) back. Slap the PCs with something suitably nasty and debuff them some. Then tell them that the only cure can be found in the Orcish lands. Smile evilly when you do, they earned it.
Of course people aren't the only ones to get sick. Player's mounts and familiars could come down with a nasty case of "poops in your shoes". Nothing like a semi-intelligent animal with a case of the flu and a surly attitude because of it.
In a more modern day, or even a futuristic science fiction setting, computer and technology viruses are fair game as well. Recall that Shadowrun data retrieval you did last week? If you do then you already know why your cyberdeck and cyberwear are all on the fritz. The alien artifact you found on Planet LV-426? Infected with an intelligent AI virus that is going to try to turn your ship, and your crew into its mindless slaves.
Hard technology isn't the only target here. Biotechnology is just as susceptible to illness as we are. That spine gun could stop regenerating ammo, or your spinal tap could suddenly cease increasing your intellect and instead inflict a little madness. Magical items could easily far prey to a magical disease. Eww, why is my rune sword of demon slaying oozing green mucus? Never a good thing.
OK, in hindsight, yes, being sick sucks, but you know what they say, "Misery loves company."