MultiPatch all day every day. It's better at applying patches than creating them though. The latter works but is somewhat limited. It can create IPS, UPS, and XDelta though so that's mostly what you want to use anyway. It works at least up to El Capitan, I haven't any knowledge of any OS after that.
For SNES headers I just run TUSH in a wineskin. No config needed IIRC (if there is it's corefonts and dotnet20). Other stuff I know works in a skin:
-Temporal Flux, with dotnet20 and AFAIK corefonts. You need to run it in a Virtual Desktop.
-YAPE needs no config. I've run into problems with the OSX port of Gen III Hacker Suite however (which is buggy anyway).
-Randomizer related: Oblige runs with no config needed.
-FFPatcher Suite: Everything but FFOrgASM requires corefonts and dotnet20. FFOrgASM is a no-go because of the dreaded dotnet40.
Currently working on FF3USME, but I'm unsure of what it's built from so I'm having troubles with the winetricks (the OSX FFVI tool won't cooperate for some reason). An important note: it appears .txt files made with TextEdit use text encoding that breaks when looked through a browser. Using LibreOffice gets around this pretty easily. I learned this the hard way with Chrono Trigger and just recently got to the bottom of the problem (I think).