Rev. 16:3 KJV And the second angel poured out his vial upon the sea; and it became as the blood of a dead man: and every living soul died in the sea.
What is "every living soul died in the sea" referring to?
Revelation is a highly symbolic book, but it, at times, gives us definitions to use for its own symbols. Let's start by identifying the potential key symbols. Excluding the verbs and focusing on just the nouns, they are:
angel
blood
dead man
living soul
sea
vial
Of those terms, the most important two when it comes to answering the question Daryl has asked, are "living soul" and "sea." Understanding them will help to open up the others.
Let's start with "sea": What does the Bible say it is?
Revelation
7:2 And I saw another angel ascending from the east, having the seal of the living God: and he cried with a loud voice to the four angels, to whom it was given to hurt the earth and the sea,
7:3 Saying, Hurt not the earth, neither the sea, nor the trees, till we have sealed the servants of our God in their foreheads.
Here we see two non-sentient entities spoken of as being "hurt," including "the sea." How could it be hurt if it consists merely of water?
12:12 Therefore rejoice, [ye] heavens, and ye that dwell in them. Woe to the inhabiters of the earth and of the sea! for the devil is come down unto you, having great wrath, because he knoweth that he hath but a short time.
Who inhabits the sea? Do people really live in the waters of the sea?
13:1 And I stood upon the sand of the sea, and saw a beast rise up out of the sea, having seven heads and ten horns, and upon his horns ten crowns, and upon his heads the name of blasphemy.
Do we understand this to mean this beast just emerges from nowhere, out of "thin air" so to speak? Or what does "the sea" here mean?
17:15 And he saith unto me, The waters which thou sawest, where the whore sitteth, are peoples, and multitudes, and nations, and tongues.
So "the sea," from which the beasts of Revelation emerge, represents peoples, multitudes, nations, and languages. I believe the closest one-word equivalent to summarize all of this might be "commerce." Consider, for example, what Revelation itself says of the sea next:
18:17 For in one hour so great riches is come to nought. And every shipmaster, and all the company in ships, and sailors, and as many as trade by sea, stood afar off,
18:18 And cried when they saw the smoke of her burning, saying, What [city is] like unto this great city!
18:19 And they cast dust on their heads, and cried, weeping and wailing, saying, Alas, alas, that great city, wherein were made rich all that had ships in the sea by reason of her costliness! for in one hour is she made desolate.
18:20 Rejoice over her, [thou] heaven, and [ye] holy apostles and prophets; for God hath avenged you on her.
18:21 And a mighty angel took up a stone like a great millstone, and cast [it] into the sea, saying, Thus with violence shall that great city Babylon be thrown down, and shall be found no more at all.
Babylon in the midst of the sea? Yet that is precisely what the current world of commerce is, isn't it? Confusion. A bedlam of noise. Stock market ups and downs, trade embargoes, capitalism, monopolies, insider trading, rich and powerful, poor people just trying to eke out a living, etc.
Obviously, many people, of many nations and languages, will be in heaven, right? But . . .
21:1 And I saw a new heaven and a new earth: for the first heaven and the first earth were passed away; and there was no more sea.
. . . there is no "sea" in heaven! It's gone. Just like there are no "dogs" in heaven. "They shall not hurt nor destroy in all my holy mountain: for the earth shall be full of the knowledge of the LORD, as the waters cover the sea" (Isaiah 11:9).
Only three texts in the Bible use the term "living soul" in the KJV translation. They are as follows:
Genesis
2:7 And the LORD God formed man [of] the dust of the ground, and breathed into his nostrils the breath of life; and man became a living soul.
1 Corinthians
15:45 And so it is written, The first man Adam was made a living soul; the last Adam [was made] a quickening spirit.
Revelation
16:3 And the second angel poured out his vial upon the sea; and it became as the blood of a dead [man]; and every living soul died in the sea.
The first two texts clearly refer to a perfect creation, a sinless man (Adam). When Jesus saw the Jewish leaders of His day, He spoke of them as "whited sepulchres, full of dead men's bones." Conversely, He referred to the entombed Lazarus as yet being alive. What, then, is "life" in God's sight? It is spiritual life; eternal salvation. People may have physical life and yet be "dead" to God.
Those who are caught up in the world of commerce will lose their spiritual life. They will lose their salvation. This, I believe, is the primary meaning of the text of Daryl's question.
Blessings,
Green Cochoa.