I can totally get behind that comic books and FR have a lot in common. My dislike of playing and running FR is best summed up with the DCURPG I tried to run in the early 2000's even though it has nothing to do with Forgotten Realms.
We were using the Westend Games d6+cards rule set. We had real comic experts, we had a person who had never read a comic, and pretty much everything inbetween...yet we had 2 major blow ups and 2 medium size misunderstandings that I think are important to show why games with large lore and character benches are a problem.... and the best part is we thought we side steped them all...
I was running the game for 6 players. We agreed to do an amalgam of Batman Beyond and the cartoon universe. I had in my mind the set up for a slightly changed version of the JLA 2 parter to have happened, and the JL disbaned (hawkman dead, and GL leaving earth for a long period) leaving the world without a league... first minor problem came with that pitch, 2 players (one very vocal and charismatic who got others to agree) didn't want to form a justice league...even if they would be the only, and biggest team they wanted a different name. I agreed and said "Can we make a new Titan team then?" and my pitch got modified to them all being high school students... OK so now we have our game and everyone is talking about characters and we can start character creation night.
1st issue(Major size misunderstanding) I say we will begin in New York highschool. One player (who reads comics far more then I was at the time) says "If we are going to be titans isn't that the wrong coast? so rather than go point by point over the course of 2 real life weeks we argued back and forth (on game night and other nights) I said Titan tower is in NY, he said San Fransisco bay... long story short we were both right. When I was reading in the 80's and 90's it was in NY, what he was reading now it was in SF, and we both had comicbook proof...
2nd issue (Medium miss understanding) one player (who didn't read comics) pitched his idea for 'Donald Parker' who was descendent of peter and had a tech based spider suit... he asked why the 90's spiderman series of cartoons (and for that matter that area x-men) couldn't fit with batman beyond timeline, since they were all in comics together.
OK, so character creation was weird... our 6 players ended up as pretty much spiderman and rogue, a ghost of a sucide teen, a guy who's powers were radiation control and self resurrection, a half white Martian (so super str, flight, shape change and telepathy), and a green lantern...all teens going to highschool
3rd issue came game 2 (medium misunderstanding) The bad guy was Lex Luther's daughter, and current CEO of Lex Corp. They knew she was the bad guy but couldn't prove it... this lead to multi weeks of not getting how to have a superhero game, and lots of "Why doesn't superman heat vision Lex" discussions. This problem came in the form of D&D players not quite getting the superhero thing..
4th issue came end of game 3 or 4 while still wrestling with 3 and having gotten a good laugh at the end of 1. (Big blow up) The first time I brought NPCs in from the comics. So I had two NPCs who were twin girls. They were nerdy students at the school but become (super hero form so on/off powers with physical changes in looks) superman like beautiful heroes. They had flight, invulnerability (kryptonite and magic weakness) enhanced str, speed, endurance, and energy blasts from hands and minor TK, and telepathic defenses that also allowed them a telepathic bond... Everyone was super happy to have them join the team, and find out the mystery of where these semi telepathic kryptonians came form... So being a nerd I introduced there parents. There father had the body of the kryptonian Eradicator (Last son from 4 supermen story) but the mind of a star labs scientist...there mother was Maxima. They split there time between here and an alien world(maxima is queen of said world almanac I think) but are allowing there children to live and be raised here... I thought it was cute, and would open up off world adventures. OPPS... from this moment of revelation I got instant "Hey if maxima is around does that mean Captian Atom is...what about Firestrom (they were all in extreme justice togather after all)" so I had to start figuring out what was and was not cannon...no big deal. Until the first time I brought a villain in after this. Very first thing I heard was "We should call Maxima and Eradicator in" followed by "Hey did your mom ever give you access to her old JL communicator, we should try to call the old JL...even if they aren't able to help some of them should have kids with powers..."
If you act like Elminster and the 7 sisters are not there, you may get away with it...once you start to hint at them in the least you could have the same issue as issue 4... "Wait, if this is important why aren't..." issue 3 I don't think can directly be used as a FR issue, but 1 and 2 are perfect fits for any setting with movies, books, or just too much lore...if you don't all have the same level of understanding missunderstandings happen...
You know what I found elemenats all 4 issues. Make up your own setting.
Its simply don't involve major NPCs without a plan ahead. Most of the time unless you have a clear use for them, just don't use them, tell the players they are indisposed with personal issues.