Just watching Big Bang Theory. Johnny Galecki’s character, Dr. Leonard Hofstader, has had a one-night stand with Sara Gilbert’s character Dr. Leslie Winkle.
This is interesting because Galecki once played David Healy on Roseanne. David was of course the boyfriend (and then husband) of Darlene Connor, played by . . . Sara Gilbert.
What other pairs of actors have played romantic couples in multiple roles?
John Wayne and Maureen O’Hara made 5 films together.
Spencer Tracy and Katharine Hepburn made nine films together, and they played romantic partners in most of them. Of course, Tracy and Hepburn were off-screen lovers for decades, as well. 
This is very common in Bollywood (Indian) movies, where an actor and actress will form a popular *jodi *(onscreen couple) and make several movies together. Some hook-up offscreen as well.
Although they never married or even dated, you’d be hard pressed to find a better match than Greer Garson and Walter Pidgeon in “Mrs. Miniver”, “Madame Curie”, and others. Here’s their first time on screen together.
Leonardo DiCaprio and Kate Winslet in Titanic and then about a decade later in Revolutionary Road.
Meg Ryan and Tom Hanks?
And I just thought of Chevy Chase and Goldie Hawn in Seems Like Old Times and Foul Play.
Seeing as how this example is most likely (IMO) “just” a casting gag, what do you consider to be “fated” and not “just a casting gag”?
For example, would a number of castings put it over the edge? Separation of time? Obscurity of a previous pairing? Format (since such things are easier with TV than with movies, for example)?
Fred and Ginger made 10 films together.
Geena Davis and Jeff Goldblum were in three films together playing a couple and got married.
William Powell and Myrna Loy top the list:
6 thin Man movies but a total of 14 pairings in all.
Also Andy Rooney and Judy Garland had many movies together. 9 Total.
Nelson Eddy and Jeannette Macdonald made 8 films together.
Elizabeth Taylor and Richard Burton made 3 or 4.
Bing Crosby and Dorothy Lamour made 7 “Road” pictures, (Zanzibar, Morocco, Singapore, Bali, Rio, Hong Kong, and the one where they went to Alaska). Unless I am forgetting one.
Bogart and Bacall.
I don’t care enough to look, but how many have Brangelina been in? (Mr & Mrs Smith, but it seems like there were others)
Woody Allen & Diane Keaton
Steve Martin & Bernadette Peters had a couple, The Jerk and Pennies From Heaven
I suspect you meant Mickey Rooney. 
Andy Rooney would give a completely different performance.
“Didja ever notice how the kids in these movies always solve their problems by puttin’ on a musical? I don’t like musicals. No one really breaks into song like that.”
:lol:
Not the first time I did that either.
LOL.
Mickey Rooney’s character was named Andy Hardy.
Good point! It makes What Exit?'s typo more understandable (though no less funny).