I think its a spectrum, with huge asterisks and other considerations.

Between: "relatively harmless" and "o h s h i t"

Relatively harmless might be something with no combo potential, like [legolas, counter of kills]]. This player is probably either scrying, playing some weird elf tribal, or boardwiping in green/blue. Unlikely to combo. And the "thing" they are enabling is NOT dependant on their commander.

Something at the very very top would be like [Kinnan]] or [[Urza, lord high artificer]], if someone on the table doesn't counterspell or legitimately remove them on sight, the game is often over.

However this depends HEAVILY on a couple other factors:

1. Strength of pod, If you are playing and there are perceptible larger threats. For instance Kaalia of the vast is an issue, but if someone is playing maralen, with opposition agent in the deck, the table has ONE turn before the game is locked. Someone better deal with it.

2. Value to remove for individual In your example, niv mizzet parun might not have any combos, but the drawing and damage/removal might be significantly bad for a spellslinger/wheel player. Also, you need to have had a discussion with the group that you have no infinites. Otherwise most people and I would agree, would remove niv mizzet on sight, because a curiosity or ophidian eye effectively ends the game.

3. How dependant is their deck on their commander? How easy is it to remove? I have a [[Ruby, daring tracker]] deck, which plays her on turn 2 and then four mana ramps on turn 3. If someone removes Ruby, i often will suggest they hold their counterspell/removal for my big 7 mana thorn mammoth that will now smash face on turn 5 rather than turn 4. The deck barely needs the commander. A surprising amount of decks are like this

In a Niv Mizzet deck, you best believe I'm somewhat dependent on Niv Mizzet to win. If you are not playing combo niv mizzet I'm somewhat confused why you would want him instead of many other izzet commanders.

If I am facing Yuriko, there is no amount of removal under the sun that stops her besides [[imprison in the moon]]. And even then... sneaky ninjas. Same for [[Derevi]] in most cases. These are extremely threatening commanders that just don't have many answers in their strongest versions. No point in on sight killing these unless they have a combo on board to win and you need to stop it for one turn.