If I activate Sacrifice and target my Mighty unit with a buff, can I use my Sett the Boss legend ability to save my unit and also draw 2 and channel a rune from Sacrifice's effect?

Yes, you can do this. You will successfully save your unit and receive the full effect of Sacrifice (drawing 2 cards and channeling 1 rune).

This interaction is explicitly covered by RiftJudge FAQ #10301. Here is the breakdown of why this works:

Why it works

• Replacement Effect: The Boss's ability is a replacement effect. When Sacrifice attempts to "kill" your unit as an additional cost, The Boss intervenes and replaces that event with "heal, exhaust, and recall" the unit to your base.
• Cost Paid: According to Rule 357.2.a, costs that are replaced by a replacement effect are still considered successfully paid. Because the game treats the cost as paid, Sacrifice proceeds to resolve normally.
• Buff Spent: As noted in the FAQ, the buff on your unit is spent (removed) as part of the cost of using The Boss's ability.

Sequence of Events

1. Playing Sacrifice: You play Sacrifice and choose your buffed [Mighty] unit as the additional cost to be killed.
2. Paying Costs: During step 4 of the playing process, you attempt to pay the cost by killing the unit.
3. Replacement: The Boss's replacement effect intercedes. The unit is healed, exhausted, and recalled to your base instead of being killed. The unit's buff is spent.
4. Cost Completion: Because the replacement effect occurred, the cost of Sacrifice is considered successfully paid.
5. Resolution: Sacrifice resolves, allowing you to draw 2 cards and channel 1 rune.

Note: As this is a replacement effect and not a triggered ability, it does not use the chain and cannot be responded to once the cost is paid (FAQ #5828).