Windows Installer XML (aka WiX)
It's powerful, it doesn't come with a designer, everything is saved as XML. A bunch of extensions are shipped that enable you to do IIS/SQL stuff, or else you can develop your own.
The learning curve is steep, WiX is just an XML representation of Windows Installer databases. If Windows Installer supports it, WiX supports it. If it doesn't, then you'll need an extension or a custom action.
First steps, if you want to go down the Windows Installer path is to pick up The Definitive Guide to Windows Installer by Phil Wilson. Understanding Windows Installer is key to building a beautiful, well maintained, well designed installer using WiX. This isn't some crappy book, the guy knows his stuff and explains everything in something like under 250 pages (and that includes all the .NET stuff I skipped reading!).
Best of luck :)
If you've got a very simple application and basically just need to copy a few files, I'd suggest looking at NSIS. It's very simple and you can probably have an installer done in a couple of days.
If you're developing software for a corporate environment where network rollouts are a priority, then you'll probably want to take a closer look at Windows Installer and Windows Installer XML (WiX). (Warning: a very steep learning curve - you'll want to set aside a few weeks and probably read this book to help get started)
If you want the benefits of MSI, without the hassle of learning the underlying technology then a commercial tool such as Installshield is your best bet. It's not cheap but you'll get something out the door pretty quickly.
Long term I'd advise learning Windows Installer technology. It's something overlooked by most developers, it's often seen as crazy voodoo that is overly complicated and unnecessary, in reality it's rather quite simple, just a database with a whole bunch of rules, conditions, and quirks that take a bit of getting used to :)
The best introduction to Windows Installers I've seen is Phil Wilson’s book Definitive Guide to Windows Installer. This was written in 2004 and does not have Vista or Win7-specific features.
The best site I have seen for Windows Installers is www.installsite.org. It has some introductory articles, but is targeted to experts.