A friend had this issue and I had him power down, and then reboot and one more reboot.
I have been playing League of Legends for 5 years now. Recently I had to reconnect my old stationery PC to my monitor and mouse so that I could burn a CD (yeah old school...).
I then reconnected my monitor and mouse to my regular stationary computer and after that, playing League has felt different. I feel I have major input lag (as moving and hitting skillshots seems very awkward suddenly), but I have no idea what settings might have been disrupted.
Any tips/suggestions would be greatly appreciated as this has ruined LoL for me.
I have a Predator G-Sync Monitor and a Razer Deathadder Elite mouse.