The biggest sin God cannot forgive is blasphemy against the Holy Spirit in Christianity and associating partners with God (shirk) in Islam.
Blasphemy against the Holy Spirit is the unforgivable sin as described in the Synoptic gospels (Matthew, Mark and Luke).
It's also seen as a conscious and persistent rejection of the Holy Spirit's work and an unwillingness to repent and seek forgiveness, and unlike the other sins for which one can seek forgiveness, this sin is unforgivable because it's the rejection of the very means of salvation.
Pride is the #1 worst sin among the 7 deadly sins, and is often also referred to as the "root of all other sins".
Although, some different religious traditions also have varying ideas about what constitutes the worst sin.
And in some Christian contexts, blasphemy against the Holy Spirit, which is an unforgivable sin is also considered to be the most serious sin.
And some view sins like extreme neglect or child abuse as very and particularly heinous sins, regardless of how they are classified.
Traditionally though, pride or hubris is seen as the original sin and also the worst of the 7 deadly sins, with the belief that the sin of pride leads to all others.
In some certain Christian interpretations the "unforgivable sin" blasphemy against the Holy Spirit is considered the most serious sin because it's a rejection of God's forgiveness.
And some modern religious figures as well as authorities consider actions like child abuse or even extreme neglect to be especially grave, and so they classify these sins as mortal, or particularly serious sins.
Sexual sin is also one of the worst sins but not the #1.