I'll toss another one in:

What if net-positive-EROEI controlled fusion is impossible?

We have only succeeded in producing nuclear fusion in two ways: atomic bomb primers and net-negative-EROEI reactors. Atomic bombs are technically usable as space propulsion (Google Project Orion), but the max velocities reachable are only on the order of 4-8% the speed of light. At that rate, interstellar travel is severely curtailed to only the closest groups of stars. We're talking over a hundred years to Alpha Centauri if you leave time (and reserve extra mass) for acceleration and deceleration.

Net-positive-EROEI controllable fusion is the only power source I know of that could allow anything near practical interstellar flight, so if it's not possible for fundamental physical reasons I'd conclude that interstellar flight is either impossible or nearly so.

If net-positive-EROEI fusion is impossible you could get very large, very complex, and very long lived intelligences but they'd be confined to their own solar systems.

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For completeness I'll throw in two more, though they're ones I often see discussed:

(1) They're here, and that's what (some) UFO sightings are. They choose not to make explicit contact for some reason that we are not aware of, and that all visitors have so far shared. This could include an altruistic prime directive (intervention may harm us) or a selfish prime directive (intervention has been shown in the past to produce dangerous results, like post-singularity medieval warrior kingdoms or Nazis). A second reason for lack of explicit contact might be extreme alien-ness. Perhaps they are making contact but are doing so in ways that are so goddamn bizarre that we do not recognize it or culturally process it as such. The UFO literature is full of really wacked-out tales. Maybe some of them are true?

http://www.ufoevidence.org/cases/case708.htm

Sounds like a joke, right? Or the guy was insane? But imagine a "post-singularity" (for lack of a better term) intelligence that is utterly alien trying to comprehend our TV transmissions and then trying to make contact. Might the attempt not look something like that? Like some kind of weird dada-ist staged imitation of scenes from "I Love Lucy" and "Father Knows Best" with a dash of "The Outer Limits"?

Might you not also choose an isolated subject for safety reasons? Like a farmer in a field?

Sometimes I wonder if the weirdest most "dada" UFO cases are the most compelling. I would not expect alien contact to look as rational and methodical as meetings between human cultures. We're talking about an intelligence from another biosphere here, or a machine intelligence built by intelligences from another biosphere. Their thoughts might not even be translatable into English outside of the most objective domains like mathematical physics. Consequently unless they staged an undeniably dramatic contact event, we might be likely to dismiss their attempts to communicate as episodes of madness on the part of witnesses.

(2) The theists are right. We are the special creations of (or evolution was guided by) a supreme being and are unique. This is actually a variation on the "we are living in a simulation" hypothesis when you think about it.