This was the topic of a livestream a couple of days ago. As is my custom, here is the written version. It is something I re-visit every year, so it is nice to have a historical record of sorts on how my opinion on the subject changes. I do plan to do the next couple of livestreams on the same general topic, extending it to handguns and shotguns, as well as other scenarios.
Here is where my mind is at the moment.
Historically, my "one" rifle to do everything from home defense, to hunting, to plinking, to long range precision, to ... you name it, has always been some sort of an moderately light AR-15 chambered for 6.5Grendel since I think it is still the best general purpose round in the small frame semi-auto platform we have. In principle, most large frame semi-auto platforms should be in this conversation, but with the traditional 308Win or 6.5CM chambering and 14.5" to 16" barrel (to keep the same overall length as 16" or 18" small frame AR). If you carefully look at the external ballistics, larger calibers really benefit from longer barrels. They will still have better terminal ballistics than the smaller 6.5Grendel, but I deemed the Grendel to still be enough for my purposes. I happen to have such a gun and it is routinely used for pig hunting, plinking and long range shooting. It sports an 18" medium weight barrel that is light enough to carry, yet stiff enough for precision. It is exceedingly likely to end up the frst hunting rifle for one of my kids. Last year, I have serious thought to replacing it with 6 ARC, so I built myself a similarly configured 6ARC. While it is a better long range cartridge, I eventually decided to keep both, since I have two children. These are great mild-recoiling calibers to teach kids on. More importantly, they can keep using them as they grow up and never change if they do not want to.
If I lived in a suppressor-less world, there is a good chance I would continue sticking with the 6.5Grendel despite all the new developments for the time being. However, sicne I moved out of California, I have developed a ton of appreciation for suppressors. Arguably the most important application of suppressors for me is home defense. With properly designed bullets, subsonic Blackout is an excellent home defense option that will not give you permanent hearing damage.
I also discovered that I really immensely enjoy shooting long range with subsonics. It is extremely challenging and does not require a terribly long range. At 800 yards, hitting a plate with a subsonic bullet is no picnic.
One of the consequences of that is that I am looking to use the shortest possible barrel without sacrificing terminal ballistics too much. With suppressors adding somewhere between 6 and 9 inches to the barrel length, I would really prefer something with a 12" or so barrel. However, while the ATF is threatening to ban pistol braces, the best way to go about this is not clear. I do not have any interest in doing Form 1 on anything, so I am in the wait and see stage. With 30cal and maller bore rounds, in principle, I can always get GP7 suppressor from Griffin. It comes set up for pin-and-weld applications in mind. Ideally, I would prefer to stick with Q suppressors that have worked well for me. I have the Trash Panda and Jumbo Shrimp that I am very happy with.
However, with most traditional cartriges we run into terminal ballistics issues resulting from lower velocity out of shorter barrels. In the last couple of years, there has been some developments intended to overcome that, namely Sig's 277Fury and Q's 8.6Blackout. Both are of interest to me for a variety of reasons and both tackle the short barrel issue in different ways.
277Fury runs at unheard of operating pressures especially in its higher pressure military guise. However, even civilian spec ammo in new complex cases is fast. So impressively fast that on the surface of it, it should do out of a 16" barrel what 6.5PRC does out of a 20" tube. I am considering one for a lightweight mountain gun, for me "THE ONE" general purpose cartridge is not ideal. It is not designed to do anything subsonic and that is increasingly important for me.
8.6 Blackout, on the other hand, rather than pushing for higher speed, uses an incredibly fast 1-in-3" twist rate. That greatly increases the lethality of modern bullets at lower velocities. The limitation with this cartridge is that it is unlikely to ever be inexpensive to shoot, but that can be overcome with judicious reloading.
The ideal general purpose platform for this cartridge is probably an AR-10 style semi-auto with a suitably short barrel. There several smaller AR-10 type actions on the market, that are suitable. For the time being, my 8.6 Blackout is a bolt gun (Q's excellent Fix) and I am hunting with it this year. Once ATF's brace issues are cleared out, I will build myself a semi-auto in this cartridge. I expect it to be successful. For now, Q and Faxon are pretty much your only sources of guns and components. Discreet Ballistics and Gorilla make subsonic ammo. More is coming.
Given what I do here, I can't wrap this up without pointing out that scoping this general purpose gun is not exactly a straightforward thing and I am looking at a few scopes that might do the trick.
For the time being, I have the absolutely superb Tangent Theta TT315M on my 8.6Blackout and I do not think I can realy do better. Unless I decide to test something else on this gun, it is staying there. 
I'll set it up with a longer handguard and top rail to have space for a thermal clip-on, but that is largely it.
For a semi-auto, I would be inclined to go with a smaller scope and an offset red-dot give that is is also supposed to pull duty as a home defense gun. I would be really tempted to get either March Shorty 1-10x24 or Vortex Razor Gen3 1-10x24 or PA PLxC 1-8x24 on there. They work great with thermal clip-ons, but are not ideal for low light hunting without one. For now, that is probably my recommendation until I find a FFP 1.5-12x40 or similar design that would really be ideal for this. The choice of the offset red dot is somewhat up in the air for a moment since I want to look at the upcoming enclosed red dots at SHOT. Swampfox Kraken is the budget options that seems to work well. Steienr MPS worked very well for me as well, and there is always the Aimpoint ACRO P2 for a bit more money. I would prefer something smaller and I think we will see a couple of options soon. Shield AMS is definitely the one to watch, but there are others that have not been announced yet.
For the first time since I startd this "if I could have only one" thought exercise, I am leaning toward I gun I do not yet own, so it is somewhat tentative. However, everything I have seen to date out of 8.6 Blackout I have is extremely encouraging.
