What's the main thing about the universe that cannot be explained by science?
I very much like the answer provided by Serge Mavrodeo, who covered almost all of the bases.
However, as the number one unanswerable question, I prefer Steven Hawking’s: “Why does the universe bother to exist?”
My second favorite is “how did something come from nothing?” There have been attempts to answer this one. My view is that nothing can come from nothing. If one assumes the greatest possible void (not in size , but in concept), in which there is no matter or energy, no dimensions, strings, Branes, etc., there still must exist a law that permits the creation of universes, and that is not nothing.
My third favorite is why the physical constants are what they are and must be what they are in order for us to be asking about them. This is known as the Anthropic Principle. The Anthropic Principle raises the question of whether the universe is conscious observer dependent. This idea makes many scientists uncomfortable.
In response to the Anthropic Principle, many scientists proffer various as yet unprovable (and unfalsifiable) multi-verse ideas. That’s OK because the only evidence for the Anthropic principle is the existence of observers who measure and/or calculate the constants; whereas the idea of multiple universes turns universe creation into an ongoing natural phenomenon, one in which observers could evolve in a particular kind of universe, rather than a one time, perhaps discomfort creating supernatural phenomenon. That is, if creation is natural (as it must be), why would only one universe exist? Hence the need for the multi-verse.
There seems to be a preponderance of observable evidence that the universe had a beginning and has been evolving. Yet so far, universe creation is outside known science and resides in the realm of vigorous speculation
The multiverse has zero scientific proof. It is a hypothesis, as much as God. And if the multiverse were proven, it would not disprove God. Because the multiverse would have been created by God.