These are the settings that I've found to be best suited for speedrunning:

General options:

• Mouse Sensitivity: 100% - Higher sensitivity means creating clones faster but sacrifices accuracy, so use lower sensitivity (~90-95%) if you are still learning this game
• VSync: Off - Even with my crappy PC I experience no screen tearing, so it's not necessary
• Depth of Field: Off - Depth of field can slow down the game a bit and makes the character sprites blurry

Keyboard/mouse:

• Pause Menu: Q (instead of Esc) - You will be going to the pause menu a lot during the speedrun, and Q is much easier to press than Esc
• Memory Log: Left Shift (instead of F) - Mainly useful for the 100% run where you have to press E to open a Log/Message from Home and then quickly press the Memory Log button to close the message. Left Shift works best for me in this case
• Create Clone: Left Mouse Button, Swap Clone: Right Mouse Button - This is reversed from the default setting. I've found that pressing and holding LMB to create a clone and then releasing it and quickly pressing RMB to swap feels much more natural than the other way around. This is purely a personal preference, but may be worth trying out to feel the difference