I’m no expert (@drachenfeles understands the tech side far better than I do), but I can say that I have played for ‘quite a lot’ of hours, exclusively on singleplayer without significant problems. Eventually, as I build bigger and gather too many followers, I do find some performance degradation (but usually only within the oversized base itself) - and mostly it is something that starts fine during a session, but gets a bit worse as I play for several hours.
The only settings that I would say are essential to at least consider changing for SP are the animal and thrall taming times - at basic game rates they can be over 24 hours for a t4 thrall, and on SP the timer stops when you logout (because the ‘server’ also stops) - so it can be a good idea to shorten these timers to a level that suits you (I go for about 0.4 as that seems to work out about right for me).
There are no mods that are required to play SP, the game functions fine without. However - there are plenty of mods that are good to have if they are things you like.
Most of all, I would recommend LBPR (Less Building Placement Restrictions) as it allows greater freedom for building (kinda CE’s version of S+, as I understand it). But there are plenty of other great mods, depending on exactly what you personally want from the game.
Some others that I personally like:
LBPR- Additional Features - iirc this ‘fixes’ collisions on a lot of the benches so they take up a bit less room, but mostly I use it for a great Tavern build set, that is good in itself but is also in neutral colours, so goes well with most other sets (plus has some walls that are the same on both sides and can look good for interior walls dividing rooms)
Fashionist - allows re-skinning of armor and weapons, ability to change the appearances of your thralls etc
Arena Pier, & Northern Timber - two great mods that add additional build pieces (like half height walls/stairs, and 2x2 gates)
Pythagoras Support Beams - transfer structural support horizontally, allowing building out over a wider area than the base game allows
Immersive Armor - a whole bunch of extra armor variations, as far as I know they are properly balanced to the base game armors, but TBH I mostly use them for ‘re-skinning’ armor with Fashionist (see above)
Savage Steel - a whole bunch of extra decorative placeables and storage options (so I can have barrels of demon blood, jars of ichor and glands, bales of hides and leather etc)
All of these seem to be being regularly maintained, so (in theory) should be about as safe as mods get.
I also really like Emotes for Thralls (which does what you might expect ), but with the caveat that it hasn’t been updated in about 9 months, so use at own risk…
And I’m sure many others here can recommend other great mods if you are in the market for them But as noted earlier, you do not require any mods to play in singleplayer.
I hope some of that helps