If there's a safe choice for the best quest in The Witcher 3, it's probably the Bloody Baron storyline, a dark, harrowing, morally nebulous about a local lord meeting the consequences of his own domestic abuse. This was, in fact, the first thing that quest designer Paweł Sasko built for The Witcher 3, and it already had a massive script before the dialog was even added.
"Family Matters, Bloody Baron’s story, was the first quest I designed for The Witcher 3, on outline by Marcin Blacha," Sasko says in Twitter thread reminiscing over his time at CD Projekt Red. "First script was ~40 pages long, just the plot, no dialogs yet. Used Slavic folktales about botchling and lubberkin to enrich quest about domestic violence."
Some years back, our friends at PC Gamer ran a substantial interview with Sasko and some of the other key figures behind Family Matters, which is well worth a read if you want some greater insight into how the quest was made. But, of course, it's not the only thematically challenging story in The Witcher 3.
"La Cage au Fou, the story of Marlene de Trastamara, a wight cursed by hunger, tackles issue of eating disorder in The Witcher dressing," Sasko says in a follow-up tweet. "She’s trapped in a cycle of emptiness, and Geralt’s only way to break the curse is to sit down and share a meal with her."
In this thread, Sasko also reiterates the previous assertion that the Battle of Kaer Morhen was "hardest quest I have ever designed and implemented." Today, Sasko explains that the challenges included "complex branches, tons of variants, and new tech like traps, meteors leaving craters, and managing scripted NPCs at all times. Pure chaos. It was hardcore."
Sasko would go onto to become quest design director on Cyberpunk 2077, and is now serving as associate game director on Cyberpunk 2. That's certainly some pedigree for the upcoming CD Projekt Red game.
