Therefore - This would seem to indicate that the "result" of their living in this manner was that they rejected God, or that one of the consequences of their being prospered would be that they would cast off his government and authority; that they renounced him "because" they were thus prosperous, or because they wished to train up their children in merriment and dancing. All this may be true in itself, but that idea is not in the Hebrew. That is simply "and they say" - ויאמרו vayo'âmarû. So the Vulgate; the Septuagint; the Chaldee - ואמרו; and the Syriac. The word "therefore" should not have been inserted. Job is not affirming that their mode of life is a "reason" why they reject the claims of God, but that it is a simple "fact" that they "do" live, even in this prosperity, in the neglect of God. This is the gist of what he is saying, that being thus wicked they were in fact prospered, and not punished as his friends had maintained.
They say unto God - This is the language of their conduct. Men do not often formally and openly say this; but it is the language of their deportment.
Depart from us - This is about all that the wicked say of God. "They wish him to let them alone." They do not desire that he would come into their habitations; they would be glad never more to hear his name. Yet what a state of mind is this! What must be the condition and character of the human heart when this desire is felt?
We desire not the knowledge of thy ways - We have no wish to become acquainted with God. His "ways" here mean his government, his law, his claims - whatever God does. Never was there a better description of the feelings of the human heart than is here expressed. The ways of God are displeasing to people, and they seek to crowd from their minds all respect to his commandments and claims. Yet, if this is the character of man, assuredly he is very far from being a holy being. What higher proof of depravity can there be, than that a man has no desire to know anything about a pure and holy God; no pleasure in becoming acquainted with his Maker!

They say unto God - This is the language of their conduct, though not directly of their lips.
Depart from us - Let us alone; we do not trouble thee. Thy ways are painful; we do not like cross-bearing. Thy ways are spiritual; we wish to live after the flesh. We have learned to do our own will; we do not wish to study thine.

Therefore they say unto God, Depart from us; for we desire not the (g) knowledge of thy ways.
(g) They desire nothing more than to be exempt from all subjection that they should bear to God, thus Job shows his adversaries, that if they reason only by that which is seen by common experience the wicked who hate God are better dealt withal than they who love him.

Therefore they say unto God,.... While in health and life, amidst all their outward prosperity, and because of it; for worldly riches have this tendency, to make men proud and insolent, and not only to behave ill to their fellow creatures, and to slight and despise them; but even to forsake God, and lightly esteem their Creator and benefactor; yea, even to kick against him, and oppose him, to set their mouths against him, and speak very contemptuously and blasphemously of him, as in the following words; which though not expressly uttered and pronounced, which yet may have been by some, however are conceived in the mind, and inwardly spoken; and by their lives and conversations outwardly declared and abundantly proclaimed:
depart from us; not as to his general presence, which cannot be, and without which they would not be able to subsist; God is everywhere, and near to everyone, and all live, and move, and have their being, in him; nor as to his spiritual presence, which wicked men know nothing of, and are unconcerned about; but they do not choose to have him so near them as that their minds should be conversant about him; they do not care to have him in their thoughts, they are desirous if possible of banishing him out of their minds; they would live without thinking of God, or thinking that there is a God in the world, for such a thought makes them uneasy; they do not love to have their consciences awakened by him, so as to check and accuse for what they do; they had rather have them cauterized or seared, as with a red hot iron, and be past feeling, that they may go on in their sinful courses without control: this is the just character of a worldling, who is afraid he shall be a loser by God and religion, should he attend thereunto; and therefore, as the Gergesenes for a like reason desired Christ to depart out of their coasts, so such desire God to depart from them, Matthew 8:28; and of the epicure, whose God is his belly, and that only; and most righteously will it be said to such at the last day, "depart from me"; this will be a just retaliation:
for we desire not the knowledge of thy ways; the ways which God prescribes, directs, and enjoins men to walk in, even the ways of his commandments; these are unknown to men, until shown and taught them; but wicked men do not desire to be instructed in them; they have no pleasure and delight neither in them, nor in the knowledge of them; they fancy there is no pleasure to be had in them, and they think they have got into a much more pleasant way, which they have chosen, and their souls delight in; though destruction and misery are in it, and it leads into it: they wilfully affect ignorance of the ways of God; they do not care to come to the light, lest their deeds should be reproved, their consciences be made uneasy, and they not able to go on so peaceably and quietly in their own ways.

Therefore--rather, "And yet they are such as say," &c., that is, say, not in so many words, but virtually, by their conduct (so the Gergesenes, Matthew 8:34). How differently the godly (Isaiah 2:3).
ways--The course of action, which God points out; as in Psalm 50:23, Margin.

Therefore - Because of their constant prosperity. Say - Sometimes in words, but commonly in their thoughts and the language of their lives.