I have no idea what difficulty to play on. I assume Easy, but I'm not sure. I'm going to learn Any% first I think. Also, besides the scroll wheel, can I rebind anything else?

Yes most people speedrun Dishonored on Easy although there is nothing preventing you from doing a run on a harder difficulty for fun if you want.

You may rebind whatever you want in the options, for example I have "drink mana potion" bound to a button on my mouse, and the powers menu bound to T so they are faster accessed. The only thing rebinding scroll wheel in the ini file actually does is allow you to have multiple keys associated with the same action, which is useful for picking up items, as well as jumping rapidly, which allows skipping the start of the dream sequence.

I wrote a LiveSplit plugin which can keep track of your mana and might be helpful for learning mana routes. No one except for me is really using it (and I do not stream at the moment), but it is something I made somewhat recently, and I have not really told anyone who runs Dishonored about it before now. If you are interested it can be found here: https://github.com/Som1Lse/LiveSplit.ManaTracker The source code is also available.

Any% is run on easy to make the mana route faster because more mana from pots but I did do a 'Very Hard' run if you're interested;

Thanks everyone! I appreciate the quick feedback! Also, I found some super duper useful info for people with low FPS problems. In addition to all the settings I've seen edited in the ini file, it's also INCREDIBLY useful to lower the resolution to something like 1280x720. I did that and my FPS shot up from 190 average to hitting max, and I was getting elevators like cake afterwards.