Badly written and irrelevent opening narration crawls with scruffy looking art is definitely one for me. The art being stylised in some opening narration sequences (like say Zelda: Wind Waker or Undertale) shouldn't be an excuse to do really scribbly art, or to try digital painting for the first time ever with no idea what you're doing or to throw a horrible photoshop filter over it. It just makes a really bad first impression.
Hard to read text, poor text formatting and bad font choices have been mentioned a bunch of times in the thread already. Yeah... Just... ugh. Please, put some effort into making your comic readable.
Traced or copied art. Sometimes I see a comic that at first glance looks remarkably well-drawn (it especially might have a strikingly well-drawn character on the cover, often weirdly paired with a very amateurish font and background), but as soon as you try to read pages you can't help but notice that the art is really sparse and inconsistent with a lot of panels that use generic stock images with a text overlay, the same character seeming to change in how they're drawn from panel to panel, parts of characters being really well drawn with perfect perspective and crisp detail while other parts of them look floppy and poorly-defined or different characters look like they came out of totally different comics, and the poses or expressions don't quite seem to reflect the tone of the dialogue. Sometimes the angles characters and backgrounds are drawn from don't match, or even if they do, there's just a weird mismatch in detail level or style that feels "off".
It not only harms the overall immersion and visual storytelling, it just generally feels like "ugh" when the artist is avoiding using art to express themselves and worse, stealing from other artists. I'd legitimately rather read a comic that was drawn to amateur standard but with consistent care and passion and a desire to improve than this.