My opponent has Karthus and his Ruined Rex dies - triggering his Deathknell "Deal 4 damage to a unit" twice. If I respond to the target with Not So Fast, does that counter both triggers of Deathknell? Or are they separate instances?

According to RiftJudge FAQ #10983 and FAQ #9480, you cannot counter both Deathknell triggers with a single "Not So Fast" effect.

Why this happens:

1. Separate Instances: When you control Karthus, Eternal, his passive ability creates an additional instance of the Deathknell trigger on the chain. Because each trigger is an individual item on the chain, they must be interacted with separately.
2. Targeting: A card effect that says "Counter target triggered ability" targets only one specific item on the chain.

The Sequence:

1. Trigger 1 and Trigger 2 are both placed on the chain as separate, pending items.
2. If you play "Not So Fast" (assuming it targets a triggered ability), you must choose one of those two specific Deathknell triggers to counter.
3. Once the first trigger is countered, the second trigger remains on the chain and will resolve normally.

To stop both Deathknell triggers, you would need to use a counter effect twice.