I think, as far as sequels go, the spiritual successor should either be in the same time period, but in Chicago or New York or some place like that, or in the 70s, following the trail of the Zodiac killer. If it was in the same time period, however, I believe people would complain that it was more of the same, even though I would still enjoy it. So, if it were in the seventies it could still be the same basic stuff, but they could pull from different films, like Dirty Harry and Bullit, giving it an altogether different tone. If it were in the 70s, it'd have to be in San Francisco, no other place would be as cool. I loved L.A. Noire, but there's not doubt that there are some things they could have done better. I think that if they kept working on it and refined it, the sequels would be awesome.
I would love a Vegas "L.A." Noire during the Rat Pack era, when the Mafia ran the city. Cliche, I know, but still. I don't believe you need a link to any real cases (Zodiac Killer, The Black Dahlia murderer etc) to make an excellent game. Besides... I'm sure Las Vegas had plenty of "big things" around that time.