I am not talking about a role someone took early in their career while they were trying to establish themselves and get work.
I am talking about that WTF were they thinking role that made you look at the actor differently from that moment on?
I will start with the easiest one.
John Wayne - Ghengis Khan.
Wayne was already a big star when he played Genghis.
I’m going to say Meryl Streep as Lindy Chamberlain - I can never take any claims of her acting ability seriously after her complete and utter butchery of an Australian accent in Evil Angels, or whatever you yanks called that film.
Brando in The Missouri Breaks (1976) is going to be hard to “bottom”. 
Wasn’t that the point of the OP?
I’ll contribute Tim Roth playing Sepp Blatter in the just-released FIFA movie United Passions.
That is the best example. Here’s an article about the movie, The Conqueror, for anyone not familiar.
For my choice, I haven’t seen the movie yet, but Emma Stone as Allison Ng, a one quarter Chinese and one quarter Hawaiian descent character in Aloha makes me wonder what was going on.
Paul Newman took out an ad disavowing his “work” in The Silver Chalice (1954) Official Trailer - Paul Newman, Jack Palance Biblical Epic Movie HD
Isn’t it a plot point that the character looks neither typically Chinese nor typically Hawaiian, but rather feel alienated because her appearance and self-identified race don’t match.? Having someone like Grace Park play the role would defeat the point.
Henh? That’s a fun film.
I’d think the best answers would be like Welles in “Transformers”, Raul Julia in “Overdrawn at the Memory bank” (though admittedly that was one of the films where I wanted the Bots to shut up so I could hear)
Denzel Washington in “Carbon Copy”, stuff like that…
Yes, I read the OP wrong.
Watching Sean Penn in I Am Sam was a painful experience, turned into an impossible one after Tropic Thunder.
That was my point of the thread. This wasn’t a role Wayne took because he was just starting out. He took it after being an established star, hence the “WTF was he thinking”?
This, to me, is the oddest choice he could have made in his career at the time.
ETA: someone beat me to it.
Robert DeNiro - Focker F-I-L.
Sean Connery – Zardoz.
If you consider train wrecks entertaining, sure.
Thanks for posting that link. I am always amazed when I read something about “The Conquerer” I’d never read before.
It is the all-time stinkeroo.
How about Marlon Brando as the Japanese character Sakini in Teahouse of the August Moon?
Or as Dr. Moreau in the last version of The Island of Dr.Moreau?
The Missouri Breaks and Zardoz were both towering achievements in cinema damn you all!
Though I suppose one could argue that Brando and Connery might feel a tad bit ashamed ;). “The only things not on my diet would be the green top of the beet and okra.”
Certainly worth mentioning! I just hated Brando for TMB, though. He had been my hero but he began to drift into shit roles and shitty performance not long after The Godfather – with a very few exceptions.
Nicolas Cage in the remake of “Left Behind”.
It wouldn’t have been so bizarre if he was known to be a practicing Christian, but AFAIK he is not.
Christopher Plummer as the Emperor of the Universe in Starcrash.
It is a cheesy, low-budget Italian ripoff of Star Wars, and Plummer is obviously just phoning it in for a quick paycheck.
And yet he still gives a better performance than the rest of the cast combined.
According to imdb, he filmed all his scenes in a single day, and got paid $30,000 (in 1978 dollars) for that one day’s work. As a capitalist, I heartily approve.