//here is my vision of your problem solution,
//context of methods below - control derived from FlyGrid
//without invalidation
private void ChangeCellValue(Node node, Column col, object value)
{
  ChangeCellValue(node, col, value, false);
}

//with/without invalidation
private void ChangeCellValue(Node node, Column col, object value, bool invalidate)
{
  //this is a index to place data into internal data representation
  // - directly to node.Value that containing array of data to display in cells
  // as some columns can't be visible, direct way uses columns map to
  //create own map that points to internal data
  int cellIndex = GetColumnIndexForCellValues(col);
  if (cellIndex != -1)
  {
    object[] cellValues = node.Value as object[];
    cellValues[cellIndex] = value;
    if (invalidate)
      this.ActiveRootPort.InvalidateCell(node, col);
  }
}

private int GetColumnIndexForCellValues(Column col)
{
  return Array.IndexOf(ColumnCache, col);    
}

private Column[] columnCache = null;
internal Column[] ColumnCache
{
  get
  {
    if (columnCache == null)
      BuildColumnCache();
    return columnCache;
  }
}

//this method you can use when rebuild columns - restructure data in the //grid or change layout (not when columns reodered, become invisible or hidden)
public void ResetColumnCache()
{
  columnCache = null;
}
private void BuildColumnCache()
{
   ArrayList map = this.Columns.GetColumnMap();
   columnCache = new Column[map.Count];
   for(int i=0; i < columnCache.Length; i++)
   {
      ColumnFieldTag cft = map[i] as ColumnFieldTag;
      columnCache[i] = cft.Column;
   }
}

My column cache holds the column index. So ColumnCache[\"col1\"] might return 0 for example. I see your point in having the ColumnCache hold the column itself rather than the column index, however I still think that the behavior here is a bug:
If column 0 is hidden and column 1 is visible and I try to set node[1] = 1; It tries to invalidate VisibleColumn with index 1 which doesn't exist, so you don't see the value updated in the cell. I can send you a code sample that proves this if you want.

I'm not using Column.SeCellValue(Node) or Node.SetValue(Column) because you said node[index] = value is the fastest way and speed is of utter importance here

private void ChangeCellValue(Node node, Column col, object value)
{
  int cellIndex = GetColumnIndexForCellValues(col);
  if (cellIndex != -1)
  {
     node[cellIndex] = value;
  }
}

    public partial class Form1 : Form
    {
        private FlyGrid grid;

        public Form1()
        {
            InitializeComponent();

            grid = new FlyGrid();
            grid.Dock = DockStyle.Fill;
            toolStripContainer1.ContentPanel.Controls.Add(grid);

            grid.Columns.Items.Add(new Column(\"col1\"));
            grid.Columns.Items.Add(new Column(\"col2\"));
            grid.Columns.Items[\"col1\"].Visible = false;

            grid.Rows.Items.Add(new Node(new object[grid.Columns.Items.Count]));  
        }

        private void toolStripButton1_Click(object sender, EventArgs e)
        {
            grid.Rows.Items[0][grid.Columns.Items[\"col2\"]] = 1;
        }
    }