So, I'm about 290 hours into the game. I think I've finished most of the quests, found almost all locations, found all followers, books and items , etc. Are there any VERY hard to find quests, easter eggs, followers or locations?

Have you done the one with the ghost in Old Hroldan Inn ?

http://www.uesp.net/wiki/Skyrim:The_Ghost_of_Old_Hroldan

1900 hours in and I still haven't been here:

http://elderscrolls.wikia.com/wiki/Kagrenzel

Is this the one playthrough or multiple one's ?

Wow this is a really great topic and both of these that have been mentioned are news to me!

1900 hours in? I thought I was an addict. Have you combined every possible combination of alchemy ingredient pairs yet?

Still slogging through a bunch including powdered mammoth tusk, pearls, human flesh/hearts etc. Haven't even got the the crimson nirnroots yet!

Have a look around the http://www.uesp.net/wiki/Skyrim:Miscellaneous here. Most on the list are radiant quests, but there are some random unique ones too, like the aforementioned Old Hroldan inn quest.
I've had many characters, played for many hours, and still I'm not even near to doing all of the quests, there's always something new I see every time I play. And I'm glad it's so. If I did all the things in one go I'd get bored easily.

One playthrough? Yeah, right.

I've had dozens of characters.

For locations (For PC), you can check by usingthe console command

tmm 1,0,1

It shows the locations but unlike what the regular 'tmm' command does, it grays it out so it shows it but you cannot fast travel there yet

Here is also a http://www.uesp.net/wiki/Skyrim:Quests as well as a http://www.uesp.net/wiki/Skyrim:Easter_Eggs