It is now possible to disable highlights from some nicks, per buffer, or per group of buffers (like IRC servers).

A new buffer property "no_highlightnicks" has been added. It can be set easily with script buffer_autoset.py, see /help autosetbuffer for example.

If you have already opened buffer, then script option will not apply immediately to buffers. Then you can use /buffer command to manually set this property on a buffer, for example, to disable highlights from "joe" and "mike" on current buffer:

/buffer set nohighlightnicks_add joe,mike

Updated on 2010-12-02: this option has been replaced by "hotlist_maxlevel_nicks", see Max hotlist level for some nicks.