Looking for recommendations of any detective-themed point-and-click games -- AAA or indie and anything in-between, but they must be ones in which you practice the same kind of detective work and protocols that real-life detectives have to deal with, including the possibility of losing the game due to chasing red herrings or mishandling evidence, etc.

I played a lot of the Police Quest games and they felt like they could have been this, but those never quite escaped the Sierra bubble of mediocrity to be truly serious games. I suppose they weren't trying to be, anyway. I haven't played the Nancy Drew games, but the screenshots I've seen indicate they have contrived puzzles (Broken Sword-type "puzzle that has nothing to do with the story, for no reason" puzzles), and that's definitely the kind of thing I don't want. Sometimes I'm in the mood for that, but right now I'm hungry for a game that focuses on realistic protocols.

Does any such videogame exist? I want something to really strain my brain.

Blue force, and well the tex murphy games are really detective like, though there is not really a protocol.
And perhaps this if it ever comes out http://www.joystiq.com/2013/08/06/precinct-kickstarter-canceled-moves-to-its-own-tiered-funding/

I can't think of anything overly realistic, probably because I tend to think life is already realistic enough, and also quite boring, but I'd still recommend Gabriel Knight, if you haven't tried it already. It's a pretty serious game, albeit having some humorous dialogue happening quite often. It's not a detective point-and-click regarding puzzles and examining scenes, per se, but it features extensive interrogation dialogue/questioning that's very well made.

That's as far as I can think of...

[EDIT]

If you're interested, you could also try the Blackwell series, it's not particularly realistic (you play as a ghost medium), but it has a very cool system of taking notes in a notepad and relating all them yourself, which gives the games a somewhat 'detective' feel.

There's Cognition : 4 episodes

Pretty nice story, since you play a FBI agent, i call that a detective game :)

Still Life 1 & 2 too , but the first one is better ihmo... the second is, well ,kinda weird in some aspects

Discworld: Noir had pretty well designed investigating (finding clues, combining ideas, interrogating people etc.)

Gemini rue is an amazing game :)
Still life only 1 the second part is really bad
Cognition saga is good too
Never played any of the law and order games but maybe they are what you are looking for

Papers, Please ?

Sherlock Holmes games are pretty good too.

There are a couple of old threads discussing this, with some potential bits of answers in them. I could only find one, though :

http://www.gog.com/forum/general/about_sleuth_games

You should check the "forum mafia" games, too.

I'm pretty sure it's not exactly what you had in mind, but I'd recommend to have a look at Culpa Innata.

It doesn't play in the real world, but in a believable, well-designed near future. You play as a security officer tasked to solve a murder case (which, over the course of the game, develops into something far more sinister), and much of the game consists of interrogating the suspects and witnesses, and steering them towards giving you the information you need. There is protocol to follow (even an in-game officer's manual that explains what an officer is allowed to do and what he can't do), and your boss will tear strips off you if you mess up. I don't think you can actually "lose" the game, but you do get a rating at the end, which reflects how well you did your job.

The main point of the game is the complex depiction of a future that we might indeed be heading into, and it's one of the most thought-provoking games that I played in the last few years. The detective work is not the main point of the game, but it's the glue that keeps everything together and gives the game a direction. If that sounds like you might like it, give it a try, it's currently 75% off. I've also written a longer review on the product page.

Culpa Innata is good, but it lacks in the ending. A sequel was planned, but no news at all about it from years.

very good game, but it's true I'm still waiting for the sequel to know how it ends...

LA Noir - if you can get past the Rockstar Social Club / GWFL (iirc) / Steamworks protections

Not really point and click though - and maybe more action than you'd want - still... investigations / interogations...

Would any of the CSI games fit in with what the OP is looking for?

Those are the best. Nice story, good puzzles. Can't wait for the newest SH game which allow you to make more choices :)