add onclick property to appended element
<!DOCTYPE>
<html lang="en-GB">
<head>
<meta charset="utf8">
</head>
<body>
<div id="span-holder"></div>
<script>
var elem = document.createElement('span');
elem.className = "newSpan";
elem.innerHTML = "My shiny new span element";
elem.onclick = function(){ alert('Hi!'); };
var spanHolder = document.getElementById('span-holder');
spanHolder.appendChild(elem);
</script>
</body>
</html>