Fixed-width columns. They drive me up the wall; I've got a 1920x1080 screen because I like fitting lots of text on the screen, not because I want 75% of my screen to be white margins.
Links/buttons that open on middle-click. I middle-clicked because I wanted to open in a new tab, this page should stay where it is.
Sites that don't work at a DPI that isn't 72.
Those are the most immediate things that annoy me.
Maybe a better solution would be to progressively add more columns as the screen resolution allows, keeping each column at a fixed width. Doing this would be more challenging, though, than just using a single fixed width column that supports most of your users.
Links/buttons that open on middle-click. I middle-clicked because I wanted to open in a new tab, this page should stay where it is.
Sites that don't work at a DPI that isn't 72.
Those are the most immediate things that annoy me.