I have noticed that the games responsivenes degrades over time, the longer a game goes.
In particular this is noticeable in factory queues. After a while, build orders cannot be removed from the queue at all (by right-click or shift-right-click)! Note that at the beginning of the game it works just fine and after a while, it takes multiple clicks until at some point, it just stops working alltogether. Same goes for drag & drop within a factory queue. Fully stopping the production still works but has some noticeable delay.
Less noticabe but still degrading is the responsivenes of move orders for units or ACU, so that orders are sometimes not being followed and need to be issued multiple times.