It’s so hard to just narrow it down to one. A few that I’ll probably never own would be X-Men #1, Fantastic Four #1, Giant Size X-Men #1.
Daredevil #1
My holy grail comic is one I finally obtained this year a few months ago - Miracleman 3D (2D variant). Initially limited to 100 copies and printed without 3D effects so people who were color blind could better view the interior. There are not a lot of these out there!
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I think my holy grail book is Aquaman #1 (1962). I’m not much of a cape book person, but man oh man do I like Aquaman.
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Loved the miracle man comics, I collected all the warrior comics with the original black and white v for vendetta and miracle man in them…love them.
Fantastic Four #5
I love the Marvel Villain books, and with finishing up most of the ASM Villain 1sts, I’m on to Doom and Magneto.
Mine is Tec 168. I have enough for a low grade but hard to get one at a decent price.
Bone #1 or Invincible #1.
Unfortunately both well beyond my reach at this point. But I did get the Invincible FCBD 2020 double signed from the Skybound sale…
TMNT 1 for me. If anyone has one, I’ve got a recently acquired NM Hulk 180 to put towards it 
I got a TMNT #1 as part of buying my buddies collection (well keys out of it) he had it in a long box and the top 1/12 was bent down. Sent it out for pressing. Nothing I could do about color breaks but I did get the book straight. I am thinking of hitting Eastman up to draw over all the color breaks so it can’t be seen. Like fully white the top out and draw turtles on it.
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Wow nice, is it a 1st print? The thought of anyone drawing all over a TMNT 1 makes me cringe a little, but I guess if anyone should be allowed to, it should be Eastman. Not sure how much white at the top you mean - do you mean like a thick white bar across the top?
No grail anymore. I purchased iron man 55 2 years ago, and that was my big grail for my collection.
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Yeah. It has lines that go and break color all through the top of the book. Is was bent like a 7