I'm leaving this answer here for anyone else who ran into this problem, but using JavaScript.
A little background... In my company we have a 3rd party web app that used JavaScript to launch Excel and generate a spreadsheet on the fly. We also have an Excel add-in that overrides the behavior of the Save button. The add-in gives you the option of saving the file locally or in our online document management system.
After we upgraded to Windows 7 and Office 2010, we noticed a problem with our spreadsheet-generating web app. When JavaScript generated a spreadsheet in Excel, suddenly the Save button no longer worked. You would click save and nothing happened.
Using the other answers here I was able to construct a solution in JavaScript. Essentially we would create the Excel Application object in memory, then reload a specific add-in to get our save button behavior back. Here's a simplified version of our fix:
function GenerateSpreadsheet()
{
var ExcelApp = getExcel();
if (ExcelApp == null){ return; }
reloadAddIn(ExcelApp);
ExcelApp.WorkBooks.Add;
ExcelApp.Visible = true;
sheet = ExcelApp.ActiveSheet;
var now = new Date();
ExcelApp.Cells(1,1).value = 'This is an auto-generated spreadsheet, created using Javascript and ActiveX in Internet Explorer';
ExcelApp.ActiveSheet.Columns("A:IV").EntireColumn.AutoFit;
ExcelApp.ActiveSheet.Rows("1:65536").EntireRow.AutoFit;
ExcelApp.ActiveSheet.Range("A1").Select;
ExcelApp = null;
}
function getExcel() {
try {
return new ActiveXObject("Excel.Application");
} catch(e) {
alert("Unable to open Excel. Please check your security settings.");
return null;
}
}
function reloadAddIn(ExcelApp) {
// Fixes problem with save button not working in Excel,
// by reloading the add-in responsible for the custom save button behavior
try {
ExcelApp.AddIns2.Item("AddInName").Installed = false;
ExcelApp.AddIns2.Item("AddInName").Installed = true;
} catch (e) { }
}