It is a headache to find an available keyboard shortcuts in Mac OS X. I used Option + Letter and Shift + Option + Letter before, since they are preserved for inputting special characters. It has some problems:
Emacs and terminal require a modifier for Meta. I chose Command. It means if I want to use application shortcut with Command in these applications, such as Command+Q to quit the application, I have to use the right one. I always forget the shortcuts. Although I have listed them in a sheet, it is a pain to keep it synchronized with the shortcuts defined every where. I switched to a new solution using keystroke sequence shortcuts recently. All my global shortcuts start with Command+M (⌘M). A menu is displayed when I typed prefix. If I forget the shortcut, I just need to glance through the menu.