I've always envision Edward Norton as David Wong, but that may be just because I imagined the Fight Club kind of deadpan narration during the book.
As for John, I don't think anything could do him justice, so I think his character should be replaced by Brain from the old inspector gadget cartoon. There could even be a secondary love story between him and Molly.
Jennifer Lopez should be played by that girl from Gigli.

Joe Pasquale?

That is exactly what I was honestly thinking when they said shrill annoying voice.

I was thinking of Bruce Campbell as Falconer, but I can't see him being in the first movie (hell I can barely see them getting to Korok in he first movie)
Then a friend of mine suggest Campbell as Doctor Albert Marconi, I was stunned.  The fact that Marconi always seems to handle the situations with the ease and nonchalance of someone who has been dealing with demons for decades fits him so well.  The subtle allusion to Ash from Evil Dead, a look of I've been dealing with these things since i was your age, plus he would be the proper age to be a grizzled old demon killer.

My friends and I have cast this movie so many times you'd think I'd have this down but I'm drawing some blanks...

Alyson Hannigan for Amy, she could look young enough with make up, and I cannot see anyone else. (other than Kari Byron)
If age wasn't an issue I can really see the Fight Club reunion of Edward Norton as David, and Brad Pitt as John.
If you've seen Supernatural I'm guessing you can picture Jensen Ackles as John.  I know he's not really tall enough, but he's has the attitude.
I was thinking Ackles' counterpart on Supernatural Jared Padalecki for David but he is way to tall, a friend of mine offered Simon Pegg as David and I can see that.
Fred Durst has to play Fred Durst.
Taye Diggs as Morgan Freeman, because he's not supposed to actually look anything like Morgan Freeman.
I always pictured Eminem as Shitload, but he's too old now... I could see Shia LaBeouf
Jennifer Lopez HAS to play Jennifer Lopez

I could see Isla Fisher playing Amy well, if she acted a little less ditsy than she normally does.

It would be worth having the universe implode if the last thing any of us got to see was Paris Hilton, playing "Martyred Intellectual #1" being wrapped in bacon and eaten by a horrible monster from beyond space.  It would be fucking worth it.

I wasn't talking about casting Sam and Dean Winchester, I was talking about the actors.  The way they work together, and the personalities they have put forward on screen.  The character of Dean is very similar to what you describe as John, only on top of the shit ton of charisma he has the looks to help him swim in a sea of poon.  Either way they really aren't my first choices, just a couple of guys I could see pull it off.

I think Casey Affleck could easily play David.  To me he seems to be as close as Hollywood can get to average Joe.

Agreed, casting the guys form Supernatural would be both casting them to do the same thing (fight demons) and a completely different thing (do it in a hilariously inept way).

Here is a questions that pertains to this thread; what caliber of performer do you think we'll actually get for this movie?  Most of the stars listed have been a minimum of B list stars, do you really think they'll be able to cast recognized stars?

One exclusion, I could see Bruce Campbell doing this either way, because that's just the way he is.

Also, would a cast of complete unknowns be a better or worse thing?  If they were cast perfectly would that be better for the movie than the drawing power of recognized actors?

I agree, Patrick Warburton would make an excellent Uncle Drake.  I always pictured Drake as older and overweight, but he could pull off the role easily.  In any case, I stand by my picks at the bottom of the last page.  And to add to them, here are a few more minor characters:

"Morgan Freeman" - Ving Rhames:

An instantly recognizable black celebrity who fits his description in the book iirc, and would be an easy name for Dave to forget.  It'd be a pretty funny gag in the movie to have Ving Rhames playing a guy who is supposed to look just like him in real life, but whom Dave calls Morgan Freeman.

"Shitload" - Jamie Kennedy:

I mean, come on...tell me that isn't Shitload right there.

"Big Jim Sullivan" - Aaron Douglas

Of BSG fame.  Not sure how big he actually is, but that isn't all that important these days since they could just make him look bigger on film.  He has the right look though - tough, square jawed, ready to kick your teeth in, but also gentle looking.  Plus, I'm gay for Tyrol.

"Dr. Marconi" - Bruce Campbell

Yes, he's obvious.  Even moreso when you look at him in more recent roles (like the one pictured above) and see that is looking older nowdays.  He would make a perfect Marconi.

"Danny Wexler" - Ron Livingston

I don't know why, he's just always who I pictured as playing Wexler. 

I guess that's enough for now.  Of course, I demand that Fred Durst play himself in the movie.  I can't imagine he'd have much else to do lately.  It'd be nice if they brought back the Steve-O character too from the original online novel as well - or at least bring back that scene in some format with some well-known celebrity.  It was such a funny, yet powerful scene in terms of putting John and Dave's plight into context, and I was always sad it was cut from the print novel.  But anyway.  What other characters are there?  I know I'm missing a bunch, but my mind is drawing a blank right now.

I would love for the part of Jennifer Lopez to be played by someone actually named Jennifer Lopez, but not THE Jennifer Lopez.  That'd be a pretty good self-referencing gag.

Actually, a friend of mine and I were also talking about how Campbell would be a perfect Marconi (and then returning as Vance Falconer or maybe the Man in Black in the sequel).  We also thought he'd be a damn fine Wexler as well.

I do wonder if Alyson Hannigan still looks young enough to pull off Amy.  Amy is in her early 20s I think, and Hannigan is what... in her mid-30s?  It's possible, but it might be a tough sell.  If they could get her to look young enough though, yeah, she'd probably be a good pick.

Who else could play Detective Lawrence Appleton (Morgan Freeman)?  According to his description in the book, he was slightly overweight and had a shaved head and gotee.  It'd have to be a black actor who's fairly recognizable but not necessarily super-well-known.  Actually, you know who would be perfect?  Delroy Lindo.  He seems to fit the description perfectly.  Plus, he's the kind of actor who everyone sees and says, "Hey, what's that guy's name?  I know I've seen him in something else..."

Hmm... Arnie Blondestone is another pretty important character I'd forgotten about.  Dennis Farina might be a good pick, but honestly, he shouldn't be too difficult to cast.  Any generic looking older white guy with a mustache would do the trick.