With the discovery of planets around Alpha Centauri, the time for serious discussion of interstellar exploration has arrived. (And it's been going on in earnest for a while now.) Of course, the people who launch the probes will know they can't possibly see the up-close pictures of any extrasolar planets in their lifetimes. But if we're willing to set aside money in endowments to compound interest for the sake of future generations, why not do the same with long-term space travel?
A sensible approach is to send multiple small probes that behave as a network. Even if they can't reproduce, and even if they can't repair each other to some degree, this is superior to putting all your hopes into one object moving at relativistic speeds in unknown domains. It would be bad if, after millennia of waiting, your single big ship hit a comet in Alpha Centauri's Oort cloud. This is the proposal of Allen Tough and is being realized through a Cornell-initiated project now funded by KickStarter. Landers are a tougher problem, particularly on planets with thin atmospheres where we can't use high effectiveness-to-mass technologies like parachutes to slow the descent.
Human missions are much more difficult engineering problems - either of engineering the vehicles, or engineering the humans inside them. The problem of how to get humans to another star is likely to take much longer to solve than how to get unmanned spacecraft to another star. At the same time, keeping our eggs in different baskets is a good survival strategy for the long term, but that's no reason not to send machines out ahead of us.
At the same time, it's possible that if we reach other worlds similar to the one where we evolved, life (intelligent or otherwise) may already be there, and this may impact on our survival also. Consequently any program of interstellar exploration must be part of a program which acknowledges the very frightening implications of the Fermi paradox and also how to detect intelligent life, if it exists. At all costs we should avoid detection, the results of which which may be another answer to the Fermi paradox (i.e. that the Drake Equation should contain a term for predation.)
Consequently, here's a brief summary of some problems in interstellar colonization and interstellar evolution. Surprisingly, I haven't found an argument map for the Fermi paradox, the Singularity and related arguments, which is what I was initially planning to use as a figure.
1. Whatever path we take to the stars, it will likely be one that yields profit in the near term. Interstellar exploration cannot do this, and will have to be borne on the backs of ventures that produce a return for the investors and/or citizens involved, like (possibly) asteroid mining.
2. The Fermi paradox is likely to be solved by one of two things: we are alone at least in terms of intelligent life (i.e., there is a great filter in front of us) or because they exist, but we don't know what we're looking for or at. This latter option complicates things and makes the universe seem more dangerous.
3. To find places that may be useful to us and/or alien life - assuming complex replicators made of matter (will we even recognize complex replicators that aren't?) we may also assume the following are more likely than not, and constrain our search accordingly:
3a. We should look where there is more matter, and more mature stars (longer for life to evolve and expand beyond its home world). This means to look inward toward the galactic center. On Earth, evolutionary innovation comes from the equator and expands north, for a similar reason: more energy into the system, more liquid water, and more evolutionary innovation. A similar principle may describe the distribution and migration of life in a spiral galaxy.
3b. Look for places with the best reaction media to produce replicators. Standing liquid makes the emergence of replicators more likely because you're creating an environment that favors the rapid interaction of molecules. Water is an especially good solvent because of the number of combinations it allows. This isn't an aqueous-carbon chauvenist argument - if there are other environments that allow replicator building-blocks to interact more rapidly and richly, then those environments will be better places to look for life than places with water.
Basis for aqueous chauvenism: it doesn't have to be a planet-wide ocean, but we don't
3c. Suspect life in proportion to reaction volume. If we're talking about water, this means more surface area, and more depth. As origin zones, possibly liquid-water-bearing super-Earths are then more likely to originate life than small worlds.
3d. Look for places with a good reaction medium as in 3b, but with low gravity. This directly conflicts with 3c, but low-gravity bodies with water would be good places for life to spread to (i.e. Enceladus) because of the economics of shallow vs. deep gravity wells. A watery moon of a warm gas giant would be even better. In this sense, super-Earths are interstellar East Africas; places like Enceladus are an interstellar Polynesia. (Admittedly intra-Earth colonization is a dangerous analogy in this discussion.)
4. We should look for artifacts at least as much as signals. Artifacts may be easier to recognize as extrasolar better than artificial signals; and, if some form of interstellar colonization is possible, or at least exploration, we should expect to find artifacts in our own solar system already, unless we think we're the first or are somehow amazingly lucky. The presence of artifacts is also a better test for te possibility of interstellar travel than signals. If von Neumann probes are possible (or "space algae", if we can tell the difference) we should look for evidence on small bodies in the solar system, again because of the economics of gravity wells. If we don't find evidence of artifacts once we've explored even a fraction on any low-gravity bodies, and von Neumann probes are possible, then the possibility of life or its artifacts expanding beyond its home solar system is de-valued significantly. (I would put this on Long Bets but at the rate of current exploration, don't think the question will be settled in my lifetime of maybe half a century more.)
5. I've already made many huge assumptions here, and I'm being more conservative than most. It bears keeping in mind that we have N=1 and we don't know what we're looking for or at.