From one aspect, when what we fear acts on us, we are changed in ways that frighten us. A fear of heights is really a fear of splattering on the ground after falling from the heights. That's why, pace Steven Wright, no one is afraid of widths; they can't change us in bad ways.
How do things we fear change us? The same way all things change other things. A lesser thing lessens what it changes; a greater thing makes what it changes greater.
Most of the things humans fear are lesser things. Heights are physical things; they change our physical bodies from well-ordered to poorly ordered (and possibly inanimate). Man-eating tigers are animals; they change us into, at best, more tiger. Tax audits are social things; they change our social standings from one of relative security to one of relative doubt.
But it wasn't a lesser thing Isaiah encountered in the Temple, or Simon by the Lake of Gennesaret. It was a greater thing, the Greatest Thing, something so great it isn't even a "thing" in our order of being. They met the Living God (though of course Simon didn't know he was in the presence of something that great).
Since greater things make us greater, why would anyone be afraid of encountering God?
Let me mention two reasons. First, greater things don't always make lesser things greater in themselves. Ask a chicken whether it feels any greater after it's been made into a human by way of a chicken and dumplings recipe. "Look on the face of God and die" about sums up the expectations sinful man has of a direct encounter with the Divine Essence. It's not that God smites people out of indignation ("How dare you look upon Our Majesty!") or spite ("Take that, puny wretch!"), but that, in the presence of His life, we are as death; in the presence of His goodness, we are as evil.
The good news of Jesus Christ, though, is that we can look on the face of God and live -- that, in fact, God sent His Son to us so that we might look on the face of God forever and live forever with Him. This is a change in us, to be sure; not an evaporation of us in the Divine Presence, but a transformation of us into something somehow divine as well. Why would anyone fear that?
Perhaps for the same reason we might fear being eaten by a tiger. It would turn us into something we are not. It would, in fact, destroy what I usually consider myself to be, the "false self" mystics speak of. Even when we know, on one level, that all we have is a gift from God, that everything we do should be done for love of God, that the way of perfection is self-denial... even then, we often think, believe, and act to put our own selves first. We value our selves as though they were things of substance, and we know that, in the presence of God, these things will cease to be. We can say that's good and proper, but if at any level we believe we really are these things, then to us the presence of God means the death of us.
Jesus said to Simon, "Do not be afraid."
(This is a rip-off, and a riff off, of today's homily by Fr. John Corbett, OP. Whatever is good and clear in this post comes from him.)