With the recent influx of vampire crap that spawned from Stephanie Meye's horrific fairy-tale teen fappin' material, people are getting sick of vampires. In a way, I do not blame them. I even get tired of seeing my favorite dark creatures get soiled with emo/gothic teenage books that are too countless to number them all. But then again, I will find Dawnguard extremely boring of they talk about metaphysics, science, bacteria, kalpa and all those things. If I wanted to things, I could go to class and try to study rocket science. This is fantasy, not a medieval world where we can all study the intricate details of the cosmos. Sure, if that floats your boat, alright then by all means have fun.
This is an extremely debatable point, and has been debated before elsewhere, very recently. I will just say that sci-fantasy elements have been in place for a long time, although they've gotten much more attention relatively recently.
But as you said, if they don't like it, don't play it. While they were having fun playing as the Nerevarine, no one complained. There was so much to do than to play as the generic hero to save the world. When we had to fight off hordes of demons, there was plenty of other things to do. Same for Skyrim. Don't like vampires? Get in line like everybody else. Bethesda might release some ingame books where they talk about germs and micro-material within a Khajiit's whisker.
Nobody complained about being the Nerevarine because that story was compelling, and as you said, even if you didn't want to go through the main quest, there was a wide range of other things to get involved in. I don't care if some of the side quests (I mean legitimate side quests, not
Skyrim's Miscellaneous tasks) revolve around vampirism or develop it further, as long as they don't put out
Shivering Isles-sized DLC packs about a tired, dull topic. I don't think that it would pique the interests of the majority of players, casual or lore-fiends. Maybe if they did something like
Bloodmoon, where you can avoid actually being a vampire, but still. Expanding the lore in a unique direction would be much better. I think that exploring the Arcturian Heresy, or the Thalmor disassembling Mundus (and actually giving them a new, meaningful motive), or, I dunno, the
continents of Nirn going on strike would be much better than vampires.