It should depend on the keyboard layout, qwerty or dvorak and language configuration, of your main user. It also depends on the usage of the application when the user should trigger it. Is s/he using the mouse or the keyboard for instance.
On the topic of remembering a hotkey, using Ctrl S
for a save action or Ctrl O
for open is pretty much standard for GUI applications nowadays, so users would remember those. If the shortcut is used many times or is important in the application the user will remember it, even if it's as silly as pressing Shift
5 times in a row.
If it's not used often, it should be presented to the user in a way that it does not interrupt the work flow, as a shortcut is often displayed in a menu item for instance.
And as a final note, don't make a keyboard shortcut to remove your changes and place it next to your Save
shortcut. :-)