Most Noteworthy NASA Mission?

[Wetzel]

Like Eddie said, the Apollo-Soyuz Test Project, the first international manned space flight.

International Space Station Flight 2R, the beginning of human habitation on the ISS.
{Edit}
On second thought, that wasn't a NASA mission.
So I'll say STS-88, first shuttle flight and beginning of the ISS assmebly. Zarya was previously launched on a Proton rocket, and the (I think) Endeavour carried the Unity module up and attached them.
{Edit}

Wetzel
~~~~~~~~~~~~~~~
Soyuz-Apollo for you Russians out there