• The Standard Model is too successful. So far the SM works perfectly for all processes observable in the lab. We desperately need it to fail somewhere, to get any useful hint of how to go beyond it.

• We need to create or detect  dark matter particles. There are a lot of guesses as to what the dark matter fermions might be, but we desperately need to know precisely what they are, given their extreme importance in the history of the universe.  Such knowledge would  also be a gigantic clue as to how to go beyond the SM.

• We have overwhelming indirect evidence that the entire universe underwent a phase transition, known as inflation, when it was just 10^-36 to 10^-32 seconds old. We need to see direct evidence of this transition, via direct detection of gravitational radiation from that era, imprint of the radiation on the last scattering surface (CMB), or some direct effects of  inflation on the large-scale structure of the universe (superclusters of galaxies, etc.).

• One of the biggest missing pieces of physics is a quantum theory of gravity. It's not our fault, we have never seen a quantum process involving gravity! Without an understanding of quantum gravity, there is no way to understand the very, very early history of the universe. Just this year, it's become possible to create extremely large systems which are still quantum systems, and by making gravity important within such systems it might be possible to get some clues as to what quantum gravitational effects might be like.

• Albert Einstein and Willem de Sitter introduced what we now call dark energy in the early 20th Century.  Einstein used it to produce a static universe, neither expanding nor contracting, while de Sitter used it to model an empty universe which was expanding explosively.  Studies of very distant supernovae revealed in the late 20th Century that in fact the universe was expanding explosively, so that it is in effect a non-empty de Sitter universe!  Dark energy is a dynamic, inherent property of empty space, which causes it to expand.  The more empty space, the more dramatic the expansion.  Physicists know how such a property fits within Einstein's theory of gravity, but no one has the slightest idea how a quantum description of the vacuum would lead to such behavior!