Of course there is no such threat in game, but I'm talking about roleplay.

A Dragonborn who's done the MQ, or simply any character that has gotten on their bad side and is living in a homestead away from the protection of a town should expect an assault on his home in the future.

Hypothetically speaking, would s/he be safe?

In the best scenario, your spouse, steward and housecarl should be all capable fighters. It's even better if the PC is Dragonborn and can call a dragon as a backup if needed.

The Thalmor would be too arrogant to send an actual army, so this might be enough.

However, there is a second possibility. What if they simply decided to burn down your home with mage fire while your character and everyone else is sleeping?

Even the strongest person may not escape death in that kind of situation.

I can understand a homestead getting attacked by the Thalmor and its possible that your character has the possibility of getting killed. I would say no, they wouldn't always be safe and anyone can get knifed in their sleep. I'm sure their home may get burned to the ground or something like that.

But......If I were my character who is a vampire lord, doesn't have children or a spouse.

I would stay where I'd have some protection. I'd stay hold up at the Volkihar Castle for a few thousand years around my fellow vampires. I find being a vampire lord has its advantages against the living and with that castle's history, it seems it has avoided a lot of attention.

I think I would have better chances there.

Don't forget how the Thalmor work. The troops aren't their main threat; they work by more underhanded methods. Your spouse/steward/follower will turn out to be a Thalmor agent, and will stab you in your sleep. Or they'll think that you're the Thalmor agent, and do likewise.

You won't be safe until you've wiped them all out!

It would depend on the character, the homestead and what sort of life the character made for him/herself. Some would just shrug and say, "Let 'em come, I could do with some practice!" while others could have very legit worries of the Thalmor coming after his/her spouses and children. I would imagine in the latter, those characters would have to sit everyone down and arrange some sort of plan of what to do if the Thalmor comes knocking. Or discuss the possibility of moving from the homestead entirely to a walled city such as Windhelm. The possibilities are endless.

But you're right, role-playing wise there is no way the Dragonborn is going to sleep soundly knowing that he/she had made the Thalmor very, very angry with him/her.