^what orange said - depends on the size of keyboard and usecases.
For my fullsize custom I:
- switched the PgUp, PgDn, Hm, End to form a T-cluster to mirror the arrow cluster: I never understood why Hm and End were arranged vertically;
- I replaced Insert with Backspace (left handed numpad and arrow cluster means there is no backspace within reach);
- "Space Cadet" which gives a ( and a ) for single tap of LShift and RShift, respectively, is neat. Still getting used to it;
- Break/Pause is now Ctrl-Alt-Del macro (and Crt-Shft-Esc on Fn layer);
- Numlock is = (windows keyboards don't have dedicated = on the numpad =/ )
- Media controls on the bottom right Alt/OS/Menu/Ctrl cluster as I never use these;
- A cheeky arrows cluster under WASD for writing tasks;
- Down arrow under 5 instead of under 2 on the number cluster
EDIT: I also split the space with left as backspace and right as regular space - this may be outside your question but I thoroughly recommend a split space.