Hotkeys work by default for most users in n64. But you must specify which one you're interested in. lr-mupen64plus is just like any other libretro emulator and doesn't really care about the n64 controller shape. All the typical hotkeys should work the same as if you were in SNES. Since retroarch uses button values and not button labels for hotkeys.
In the case of mupen64plus, you have to realize that the only hotkeys most people use are save state, load state, and joy mapping stop(exit). There are other options, but there is no retroarch GUI for this emulator, so select+X is pointless. All of these are found in mupen64plus.cfg. InputAutoCfg.ini is only for in-game controls. Now if for some reason it's not setting up hotkeys properly by default(happens mostly to xboxdrv i think), you can disable the auto script. It's located in autoconf.cfg. Just set mupen64plus_hotkeys to 0. From there you'll be able to set up you hotkeys for good in mupen64plus.cfg without being overwritten. Autoconf.cfg can also be accessed through the configuration editor.
The format for joypad hotkeys in mupen64plus.cfg is like this J(Joypad Index)B(First Button Value)/B(Second Button Value). So pretty typically it looks like Joy Mapping Stop = "J0B8/B9". You can do multiple controllers by just adding a comma and typing out another definition in the quotes. You can do a single button press hotkey by omitting the second half of the string, /B#.