The game's launch came the same day as the mass shooting in the Washington Navy Yard and just hours after reports that the suspect, Aaron Alexis, often played violent video games.
(Read more: Alexis had access card for Navy Yard; investigators look for motive)
While these kinds of horrific shootings always raise questions about a regulatory crackdown, such events have never affected game sales.
MKM Partners analyst Eric Handler said, "I don't think that the Navy Yard shooting will stir up debate again about violence in video games. Unfortunately, that tends to only happen when a kid is involved as a shooter. I haven't heard of any outcries. ... The overriding thing is that this is someone who had a mental illness, not someone who played video games."
One gamer we spoke to outside a GameStop in Los Angeles on Monday night said that realistic games could be a safe way to avoid real-world violence.
"First-person shooters just don't do it for me anymore, that's why I'm excited about GTA, cause it gives you a different perspective. It's not just people running around shooting each other—you can steal cars, rob banks—so all the stuff you wish you could do and get away with in society," said George Lizama.
A Take-Two spokesman added that there is no research that shows a connection between people playing violent video games and actual acts of violence.
(Read more: Grand Theft Auto controversies)
GTAV's setting this record speaks to three major trends in the video game industry, which has otherwise been struggling with massive sales declines as consumers shift their spending to digital add-ons, and free or cheap apps.
First, big brands rule. During the past few years, consumers have bought fewer games, but they're continuing to spend big on established titles.
(Read more: 'Grand Theft Auto V' stands ready to break records)
Second, digital content makes games more appealing. GTAV has more digital add-ons than ever, and that makes it a better value proposition to the consumer.
And third, while people have held off on buying new consoles, with the next Microsoft Xbox and Sony PlayStation coming this fall, every year the user base with consoles grows and enables a bigger game launch.
—By CNBC's Julia Boorstin. Follow her on Twitter: @JBoorstin