The image is directly drawn from the game cover which has a bland 3D render style so I decided to change it into a comic book-ish style and play around with colors etc.
I don't draw entire comics myself (way too slow) but I do like to read them - or at least look at the images.

Can we cheat and you send me a message with the answer? I have no interest in participating and not knowing that will eat my mind for the rest of the day.

That is some amazing work! And such an informative post, too. I know this thread probably started more about the guessing than the drawing, but I love seeing great stuff like this with some insight behind the artistic process that goes into making it. I feel like I can really learn something here. Would you mind if I ask what medium(s?) you work with?

Oh, and the game is Desperados: Wanted Dead Or Alive.

Wait really? *checks google* Goddamit awalterj!!! That's not it but that's the correct answer, i'm so confused, i know that i've seen something like that before but it wasn't that picture of Desperados, probably not even a game, i'm thinking a comic or even a manga (well, an older more normal one that is),

Yep, I found awalterj's response interesting, too! I'm all in favor of process explanations. I reckon they fit the thread; I'm here for practice, and I expect I'm not the only one.

It looks like Exoanthrope just saved you from such mental torment, but of course you could always PM and ask!

Thanks, and glad to hear if I could provide any useful insight. For this picture, I used a bunch of stuff:
-A4 copy paper
-pencil
-water-proof black ink (Pentel brush pen)
-colored alcohol based marker inks straight from the refill bottles, applied via splatter / brush
-black and white wax based colored pencils
-white gouache

And you got the game right, it's Desperados - sadly not available on GOG anymore!

PS: Couldn't find any proof for it but I could swear that Kate O'Hara was based on Lulu from Giarrettiera Colt (Garter Colt), not a particularly good western but it has a very nice soundtrack so it's worth checking out, if you haven't already:
http://www.youtube.com/watch?v=01gsFRb8htE

The characters from Desperados seem to serve general clichés though so maybe it's just coincidence.

Here's a quick dirty sketch, but it should be sufficient for guessing. I'll clean it up on my own time. I've been wanting to draw this for a while, but never had the motivation, so I'll take this opportunity to get it done.

Dust, and Elaysian Tail.

I immediately recognised that. One of the best platformers in recent years.

EDIT: Ninja'd

Yup, too easy. I guess it's advancedhero's turn!
I loved the Castlevania vibe I got from that game. It was a little easy, though, even on the hardest difficulty.

I love Castlevania, never gave that a try though. Maybe I will. Well, at the moment, I'm completely addicted to Nethack. I'll play that till Wednesday, when Legend of Grimrock 2 comes out! :D Okay, gimme a minute.

Here we go! I did this really fast, but it turned out pretty good. I swear I'm a better artist if I take my time! :D

The title screen for Heroes of Might and Magic?

Castles?

(if not then perhaps Stronghold)
Oh, but of course! I should have guessed it immediately... shame on me!

Exactly! I love Might and Magic! Your go.