To me, the first 3 are no-brainers and I have no idea why they aren't made already. The last one is more niche, but would be awesome. I would buy any and all of these instantly if S&W made them.
1.) 2" barrel / 6 shot / I frame / 327 Magnum (the ultimate pocket gun). I also think if they shrank it down a bit more and made it a 5 shot I'd be just as interested, and it would be an even better pocket gun.
2.) A S&W version of the Taurus 617 - 7 shot K frame .38 or .357 snubbie with a J frame-ish grip that weighs <25 oz. Why don't they make this already?
3.) 3" 625JM (I would have bought one this week but instead bought a 3" 629 I plan to cut for moon clips and shoot .44 Russian)
4.) 3" M21
Ultimately, the first 2 are a modernization of the revolver concept. As more people carry guns, they are looking for more options and many of S&W traditional options have become antiquated. Modern metallurgy should allow for a subcompact purpose-built pocket revolver like #1, and #2 is just building the perfect belt carried snubbie.
The other thing S&W really should have done many years ago is modernize their grip design. With their current 100+ year old design, if you use a set of stocks that covers the backstrap, your hand moves further away from the trigger, which IMO gets awkward fast if you shoot DA. Ruger's guns with the square-ish grip frame that is designed to be covered by the grip are designed to provide a covered backstrap while keeping the backstrap to trigger distance the same. Both my GP100 and my LCR327 are much more comfortable to shoot than my S&W equivalents because of that modernized grip design. I'm not saying S&W should change all their guns, but I'd suggest a limited line of guns with modernized grips - maybe just a alloy frame J and K frame 357.