In "Man of Steel Bars", Clark has no choice but to leave Metropolis, because he couldn't take not being allowed to use his powers to help people while beginning to believe he's the cause of the intense heat wave. Later, Clark tells Lois he's leaving the Planet. Lois believes that Clark idolizes Superman and feels just as bad as he does. Lois tries to talk him out of leaving, but Clark has made up his mind. He kisses Lois and says "good-bye".
Even Cat Grant tries to comfort Lois.
"That Old Gang of Mine":
When Clark gets shot and has to play dead to preserve his identity, Lois begins having a mini-breakdown, sobbing as one of Al Capone's goons takes away the body of her best friend. Later she's shown walking through the Planet in a daze in old, ragged clothes. It's like her whole world's been taken away.
Jimmy's tearful moment where Perry comforts him and assures him that yes, it's okay to be sad, and yes things are going to be okay.
Mayson's murder in "Lucky Leon". And the last thing she learned is Clark (the man she loves) is Superman (the man she dislikes).
In "Home Is Where the Hurt Is," Superman is sick for the first time in his life and Ma and Pa Kent are terrified for him.
The death of Lois's clone.
Lois meeting alternate!Clark, who's bullied by Lana Lang, never became Superman, and had his Lois disappear.
In "The Night Before Mxymas," Mr. Mxyzptlk traps the world in a time loop where each time around, humanity would grow more depressed and pessimistic until they all crossed the Despair Event Horizon and destroyed themselves. An elderly man Superman saved from dying is grateful the first time around, but after a loop or two he wishes he hadn't been saved.