I usually play through at least once the vanilla version before I apply mods and honestly.... most mods don't manage to feel like they should be in the base game. However, there are mods that I consider "essential" by now, as they do improve the game overall and make my live easier.
Better Dialogue Controls - sometimes the game loses fokus on the dialog and you pick a choice you didn't wanted - not anymore.
Localized Thieves Guild Jobs - ask Delvin and Vex about jobs in city XY, get the quest, done. No more save / reload until I get corresponding jobs where I'm heading.
Unknown Enchants - seeing if I already know that enchantment or not on the item itself? Yes please.
Acquisitive Soul Gems - no more Black Soul gems filled with petty souls. Souls check for a gem their size or don't get "caught".
When Vampires attack - I hate Dawnquard for killing NPCs in town. Which is why I usually do it first. With this mod citiziens don't try to be a hero and run to safety, while guards / companions / vigilants of Stendaar will stand and fight. Doesn't make NPCs invulnerable so it doesn't always work, but when I see a complete Khajiit caravan run from their place near the stables towards Whiterun too busy to talk, I know what's happening.
Run for your lives - same goal as the above When Vampires attack, only with Dragons.
Adopting children with Heartfire. Yeah. Not a feature I was looking for. At least I long thought so. Then I found out about
KhajiitChild Maisha..... how can you not fall in love with that little brat?
Faster Mining - changes the striking animation when mining from 9 to 3 - timesaver.
Interesting NPCs - just what it's called.
Khajiit speak - absolutely fantastic immersion-wise when playing Khajiit.
Talking with Septimus Signus while looking for the Elder Scroll:
- Pay attention, yes? Khajiit will ask you a question. Now... where is the Scroll?
- Khajiit does not want to hurt you. No, that is a lie. Where. Is. The. Scroll?
Or with Farengar, the mage in Whiterun:
- The thinner the patience of a Khajiit wears, the sharper their claws become, no?
- Your tone is becoming irksome, mage, but Khajiit will ask anyway: What next?