Another one that I've suggested several times here is this:

Extended GAIA

First four ideas this assumes:
- The GAIA project is going to produce some very useful results.
- One of the ideas for manned missions to Mars (and beyond) involves spacecraft going much faster than escape velocity from the Sun, and then slowing down as they approach their target.
- We will develop some useful power source for deep space probes (RTGs are kind of expensive these days, since we seem to be out of the right isotope of Plutonium).
- We will build and test a highly directional communications system (such as laser) that will allow high-speed data communication over very long distances.

The basic idea is to build more probes like GAIA (improved as is possible by the technology advances in the time between now and then), and release them from the manned probes when they have their maximum anti solar velocity. Send at least one toward Jupiter so it can have it's direction changed to far outside the plane of the ecliptic as possible.

The parallax measurements from these missions should allow us to get direct distance measurements to bright stars in nearby galaxies, plus all the bright stars in the milky way.

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Forming opinions as we speak