Ooh, permadeath. Narsty. Keep 'em coming!

Oh, by the way; hay, jefe.

Beat your favorite shooter without touching the mouse with your hands.

Or look at the screen in a mirror (or use the mouse -especially if wireless- turned around).

Or play doom 3 and consider that you lose at the first yawn.

Or, let's get crazy : play Fahrenheit with a mouse and a keyboard !

Hey, I'm doing this and it doesn't work that bad (once you get used to it)...

Play King of Dragon Pass on a Hard long game as a war clan. If that's not enough, never allocate Magic to anything but war, never trade, and raid at least 2-4 times a year.

Beat an orc in Gothic 2 at level 1 and without scrolls of trasformation. Yes, it's doable without cheats, I used to do it all the time.

I like challenges that aren't impossible and generally just change how you normally play.

Right now I'm playing World of Mixed Martial Arts 3, a MMA dynasty game with specific rules on who I can sign to fight and how I engage in my strategy.

But here's some of my own:

- In Baldur's Gate (1, 2, or Trilogy), make a chaotic character who randomly switches between good and evil acts. Perhaps roll a 1d6 with 1-2 being a good action, 3-4 being neutral, 5-6 being evil. Only make your own character, and have a balanced party of NPC's on both sides of alignment trying to keep them together. For even more fun, try to have NPC's that hate each other and keep them from killing each other.

- In Temple of Elemental Evil, keep the five character slots rule, never use any NPC's, and keep yourself restricted to one class per character and only one dedicated healer. No multiclassing, and no using multiple classes with healing. IE) No healing Druid & Cleric. You can use any class as long as they do not have extra healing (or you spec them away from it).

- In Majesty HD Gold; never use flags. Ever. No attack or reward flags. The AI has to figure out what to do on their own. Your maps may never end this way!

- In Master of Magic; do not summon creatures or heroes. Only creatures you can build normally and heroes that appear. Additionally, you can only use one type of magic and cannot use the alchemy perk to transfuse gold into mana at a 1 to 1 ratio.

- Arcanum; Make an exclusive mage but do not use harm OR teleport. Ever. Good luck.

- Theme Hospital; See how far you can get with just five doctors on every map. I doubt you can win very much.

- Mount & Blade: Never use NPC's. Also keep Wound Treatment, First Aid & Surgery at 1 or below.

- Space Rangers 2; Be a complete pirate, killing or robbing every innocent civilian you can while avoiding potentially "good" quests you could do.

I'm sure there's more I can think up, but that's all for now.

Play To the Moon and don't cry at the end of it.

Carmageddon : respect all normal traffic regulations.

Finish Postal 2 without firing a single shot.

Is that even actually physically possible within the game?

It is :) there's no mission where you have to actually kill somebody.

Play Hitman series not as a silent assassin but as a mass murderer by killing everyone as long as the games permit it.

EDIT: mind you, I myself have not tried this, and it may not really be doable.

I have :) it's actually easier than doing it the silent assassin way...

Can't remember that one specifically, but I assure you that almost every level in every Hitman game can be finished by going on a rampage. You should try it, it's fun :) The only problematic ones are when the target runs away after they hear shots, so you have first get close, kill the target, then kill everyone else.