The G65 and SL65 have already met their ends. AMG head Tobias Moers told Car and Driver last year, "at the top of our lineup, we will follow another path." Speculation pegs a more powerful twin-turbo V8 taking the top slot; the S63 already outperforms the S65, but the V12 isn't tuned to win races. Certain AMG buyers simply want an "S" followed by the largest number available. The coupe and convertible S-Class variants could hold onto the V12 a while longer, but those two bodystyles won't be offered with the next-gen S-Class.
Moers did say that hopped-up builders in Affalterbach would "continue to build the engine for other sub-brands." Since he's not likely talking about Smart, it's possible he means Maybach, but for how long? The 18-year-old M279 engine still uses single overhead camshafts and three valves per cylinder inherited from the 1998 M137. There probably aren't enough customers to justify developing a V12 of the future. Sure, the M279 produces 621 horsepower and 738 pound-feet of torque, and only diesel locomotives come close to its power delivery and cruising attitude. But even those locomotives are more advanced.
As others have noted, we appear to be living in the End Times for big cylinder counts outside of small-volume makers. Even though Bentley uses Volkswagen's W12, Audi's already said that engine won't live to see another A8 generation. It could be the same over at BMW. BMW Blog reported last week that BMW could build the next 7 Series without a V12 option, even though BMW has to build V12s for Rolls-Royce. And Bugatti boss Stephan Winkelmann told Car Advice last September, " There will be no new 16-cylinder, this will be the last of its kind." Across the board, as he explained, the reasons are the same: "Sooner or later the legislation will force everybody to take radical steps."