(1) As TheZag said, sometimes three attributes are enhanced. Good examples: Enzymes in Venomous Gas or Radiation Infection, Cytoskeletons in Invincibility, Membranes in Farsight or Mind Link. End/Rech/Slow D-Syncs, etc.
(2) Sometimes you aren’t slotting for set bonuses so the raw value of HO’s is better. A +5 Uncommon/Rare Acc/Dam IO is 33.1% enhancement vs 38.3% for a 53 Nucleolus. So anytime you are frankenslotting or 1-slotting or not caring about bonuses for whatever other reason, you should consider if you’ll get more enhancement value out of HO’s. Examples include 1-2 slotting Microfilaments instead of Travel/Ends in your travel powers, slotting powers with 1-2 Nucs and 4-5 procs, etc.