Pretty straightforward question I have here. I get why ductwork needs to be sealed if it's in an unconditioned attic basement or crawlspace, but why is it still so important to prevent it leaking into a space where there are already vents?

Very small leaks may not matter, but anything considerable will affect your efficiency and performance. You want the air to go where it is designed to go, not into a drywalled cavity. You want your water to come out your shower head, not at various leaks along the hose, even though it all goes down the same drain....

Truth is it may not be a huge advantage to "tightly" seal ducts in a conditioned or semi conditioned space. I often harken to the 100+ year old opera house renovation where I was instructed to seal the ducts in the basement......and then cut in registers to condition the basement.
Of course you want the air to go- where you want it to go, but if it's already there leave well enough alone.