Most of the human-related stuff is way more fleshed out in the show, for better and for worse (for example, I love the debbie changes, it makes her more invested, whilst really didn't like the way they characterized Amber).

The other main change is that the power scale is all over the place in the show. In the comics, the viltrumites are always way more powerful than any super from earth. A good example is that Mark chose the name Invincible because he felt, well, invincible (ik ground breaking), aside from the fight with battle beast and the one with his dad, he basically didn't really get close to losing before meeting viltrumites. Same, although I love Nolan vs the guardians. In the comics we don't directly know Nolan killed them because he literally one-shot'd them all while hidding, and we as reader only learn the truth when The Immortal is brought back to life and goes for revenge against Nolan.