I would say it was the launch titles that put either put a brand on the map or otherwise established a new system as a must-have. These are titles that were arguably so critical to a system's early success that one could justifiably claim that said system would have failed or at least sold a lot less without it. The exact number of units they pushed is much harder to determine than a game released well into a system's life (we can easily see where a system that had a baseline of, say, 50k units per week spiking up to 100k in another week before settling back to baseline and estimate it pushed roughly 50k units). But we do know these games were hugely successful, far more so than every or nearly every title released at launch and enough to where they were attached to a very high number of units (often through bundling), and were considered "killer apps" in their day.
By this criterion, I would consider these titles the biggest system-sellers.
Super Mario Bros. (NES): Back in 1985, the console market in North America was dead. While the Famicom had already established itself well enough by that point in Japan (which never experienced the "Great Crash of '83"), people in the U.S. & Canada weren't quite ready to start adopting game consoles again. But Nintendo managed to redesign the system into something that looked more like a piece of consumer electronics, and for its full North American launch in 1986 it had Super Mario Bros. as the pack-in title for the standard "Control Deck" bundle. Words cannot describe how huge this game was in the latter half of the 80s. You had to be there. Once the NES really blew up in late 1987 and through 1988, everybody in my grade in elementary school was talking about it. When I first saw one in action, SMB was the game I saw. I was in awe. I had to have an NES. For years afterward I was all Nintendo, all the time. While Super Mario Bros. 3 is my favorite game of all time, I would say the original SMB is quite possibly the single most important game of all time.
Tetris (Game Boy): Probably the greatest and most addictive puzzle video game of all time, Tetris was one of the Game Boy's earliest hits. It even released as a pack-in title when the Game Boy launched in North America in 1989. It went on to be the best-selling version of Tetris at that point, and was the best-selling game on the Game Boy. Playing Nintendo games on the go was a big deal, but it was Tetris more than any other game that really made the first cartridge-based handheld a household name.
Super Mario 64 (N64, North America only): The N64 only had two games at launch, but it really only needed one. The first 3D Mario game was the best-selling game of its generation, and almost single-handedly carried the N64 through a very strong first few months in North America. The N64 sold almost as much in the 14 weeks it was on the market in the U.S. in 1996 as the PS1 did that whole year, and it was arguably entirely on the back of Super Mario 64. At least in terms of revenue ranking, it was the #1 game of 1996 and #2 game of 1997 according to NPD, and still had enough momentum to place #10 in 1998. The U.S. was the strongest market for the N64 by far (it bombed in Japan & Europe), and while the PS1 did eventually pull ahead of it, it was the #1 system during its first 12 months on the market. While that streak was ended by the release of FF7, which did cause a big bump in PS1 sales, that game didn't sell anywhere what Super Mario 64 did, and its legs weren't enough to keep it in the Top 20 in 1998. Super Mario 64 was owned by roughly a third of all N64 owners, a figure that was likely much higher in 1996 & 1997 when the game was dominating the charts.
Super Mario 64 was also the game that demonstrated the importance of analog sticks for 3D action games. Nintendo had the foresight to have a controller with an analog stick when Sony decided to use what was effectively a modified SNES controller, and you can easily see the difference. Moving Mario with the N64 controller was immediately intuitive. You push the stick in one direction, and Mario moves in that direction. It was such a major contrast to the clunky controls that plagued earlier games on the PS1 & Saturn (Protip: Tank controls were bad. If you like them, it's only because of nostalgia).
Halo: Combat Evolved (Xbox): Master Chief ended up being Xbox's answer to Mario & Sonic, a de facto brand mascot who was the protagonist of a major killer app. Halo CE revolutionized the FPS genre, and was so popular that it ended up by some estimates to have been attached to roughly half of all Xbox consoles sold in the system's first few months. Xbox was the house that Halo built. Without the strength of its biggest launch title to back it up, Xbox likely would have failed. Halo CE paved the way for its even more successful sequel, which made online multiplayer mainstream on consoles and set certain standards that remain to this day. If Halo had ended up being some random FPS on Mac instead, the gaming landscape of the 21st century would be looking very different.
Wii Sports (Wii): After a rough patch with the N64 & GameCube, Nintendo ended up having a huge hit with the Wii. While Twilight Princess was a solid hit at launch, it was the system's pack-in title Wii Sports that truly made it a major success with strong cross-demographic appeal. It wasn't just a tech demo. It was a fun game (I really liked bowling) that demonstrated how intuitive motion controls could be when done right. Back in 2005, several prognosticators thought the Wii would end up in third place in Gen 7, and it's entirely possible it might have if it wasn't for Wii Sports showing the system's enormous potential.
Honorable Mention: Sonic the Hedgehog (Genesis). While not a launch title, Sonic was the first true blockbuster on Sega's first (and only) successful console and was at least a major contributor to its success. While we don't have granular enough data to make an assessment for Sonic's impact, I think there's a case to be made that it was important for getting Sega's name out there after the market was truly opened up to competition after Nintendo lost key legal battles. The Sonic franchise was far and away the most popular game series on the Genesis, with few if any games coming close in terms of sales.
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