If you're only changing the first rune you set in the current system, it only takes a single click (just click on the rune you want).
If you need to highlight the first rune to change it, and then click what you want to change it to, that's two clicks (click the first rune, click the rune you want). (Twice as many clicks in highlight system.)
If you want to change only the second rune you set in the current system, it's two clicks (click the rune you want [which changes the first rune to what you wanted], and click the other rune you wanted [which got changed with the first click]).
If you have to highlight what you want to change, and then click what you want, and you only want to change the second rune, it's two clicks. (So a tie between current and highlight.)
If you want to change both runes in the current system, it's two clicks (just click each of the two new runes you want).
If you want to change both runes in a highlight system, it's 4 clicks (click one to highlight, click rune you want, click the other to highlight, click one you want). (Twice as many clicks in highlight system.)