These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Angst Dissonance: While clinical depression is a serious condition, those who don't have it or haven't experienced it first hand can sometimes find Roast Beef tiresome. He has a loving wife who accepts all his faults and dedicated friends. He's depressed because that's what the disease does, regardless of cirumstances — but often he has nothing to legitimately be depressed about.
Roast Beef has probably one of the most accurate portrayals of depression in entertainment, right down to little symptoms that don't get discussed much. So his character can be incredibly cathartic to those who have had depression, but a bit frustrating for those who haven't.
Arc Fatigue: When combined with Schedule Slip, it's a nasty combination. Some arcs wouldn't be so bad if they didn't go two weeks between updates.
Archive Binge, Archive Panic: It's been running a long time, and the fact that each strip tends to be an extremely long one with multiple jokes, scenes and panels doesn't help matters. It probably takes twice as long to get through as a similarly long-running strip.
Catharsis Factor: Onstad has received a great deal of fanmail regarding the portrayal of Roast Beef's depression for this reason.
Dude, Not Funny!: Some of the Crosses the Line Twice humor can be this. Such as how Ray takes pleasure from the prospect of a dog being shot dead. (While justified due to him being a cat, it's still dickish to say Old Yeller has a "happy ending".)
Sometimes Nice Pete falls into this, being a serial killer and all.
Magnificent Bastard: Lie Bot during the time he was disguised as Ray's Uncle Culpepper. Culpepper himself even comments on how well-detailed Lie Bot's disguise was, right to the specific brand of tobacco.
Zell and Cory. Survivors of a fire and sufferers of fourth degree burns ("no dude uh with fourth-degree burns you're considered unlucky if you live")... all over their bodies. You only see them in silhouette, but Cory's ruined face is... deeply disturbing. Zell's cryptic reference to "collecting" before wheeling away into the darkness also makes one wonder what on earth they could be collecting...
Cartilage Head looks like something out of a Tim Burton nightmare.
The high school storyline. Nice Pete was already incredibly creepy, but... yeesh.
Tear Jerker: The "what is the saddest thing" strips are clearly trying to get this reaction, and they certainly do from Philippe. Special mention goes to the arc where Phillipe got some of Ray's Born Lucky qualities and made several million dollars as a result. Teodor used some of the money to send him back to his mother, only to find that his old home has changed so much that its not really home to him any more. This eventually ends with Phillipe being visited by the spirit of his father:
"Home, she is . . . la grande illusion. She a time, no a place, an' you time here was over. Pack you bag an' go back to thees life you already 'ave. You maman she will cry . . . but that is what a maman mus' do. Life ees cruel . . . but at least eet is life, at least for a while."
At the time, because he (and the entire strip) was so underdeveloped, Roast Beef's reasons flying into space wasn't that sad. But, rereading it now... Seeing Beef say goodbye in that last panel tugs the heartstrings something fierce. His reply to Pat asking if he would be returning the spaceship soon was also quite melancholy.
If you've ever been depressed, Roast Beef's storylines in general will probably hit hard.