I figured out why Ryze is hard

E is targeted, you have to put your mouse directly on the enemy Q is a linear skillshot, you have to aim it ahead of the enemy

Most dps champions only really have to swap their cursor location between two positions on the screen: Where they are moving towards and where they want to fire their abilities, whether those abilities are targeted directly on the enemy or predicting where the enemy wants to move, but Ryze has a rapid-fire spell rotation that alternates between skillshots and targeted abilities so he has to track three positions on the screen and cycle between them rapidly with his cursor.

It didn't occur to me until now that this is probably a contributing factor to Ryze's very poor winrate and the poor accuracy of many Ryze players with their Q's despite his Q being a fairly basic linear skillshot like many other abilities, and one with a pretty wide hitbox.