Do you intend to work in 2D or 3D?
This question will narrow the playing field by 50% immediately, and is the one you need to ask yourself first. Will you be working in 2D animation, creating cartoons or web interactivity, or will you be creating three-dimensional rendered animations? Very few programs can do both, though some 3D programs can use tricks of shading to create the illusion of line-drawn 2D. For 2D the choices range anywhere from Toon Boom to Flash to DigiCel Flip Book, while in the 3D range you could try Maya, 3D Studio Max, Poser, iClone - the list goes on.
Are you a hobbyist or a professional, an expert or a novice?
Depending on your skill level and level of use, you'll want to pick software that matches your ability - or even software that you can grow into. If you're just doodling around for fun or just learning, programs like Flip Boom are affordable and give you a quick taste of onion-skinned 2D animation targeting children and novice users. If you're just looking to animate a few GIFs, ULead GIF Animator or Beneton Movie GIF might be more up your alley. On the high end of the spectrum you get programs like Toon Boom Animate and Flash, both of which have somewhat steep learning curves but provide a great deal of professional functionality. Hovering around the mid-range you'll find things like Anime Studio (Debut is a bit easier than Pro) and The TAB Manga.
What's your budget?
Breaking news: Flash is expensive. I know, right? You can get discounts for student editions, but it's still a little painful on the pocketbook. For some that's not an issue, and it's worth every penny. For others, especially hobbyists, it's a big issue. The good news is that there are fully featured animation packages in the $99-200 range. The first few that come to mind are DigiCel Flipbook and Anime Studio Pro (my choice, as it offers bone systems). There's also the Personal Learning Edition of Toon Boom Digital; can't get much cheaper than free.
Do you want a more traditional feel or a more digital feel?
This applies mostly to 2D, but there's no denying that some programs, like Toon Boom Digital and Flash, offer a feel that's not quite synonymous with traditional 2D animation. If you'd rather not adjust your preferred workflow for digital methodologies, programs like Digicel Flipbook offer a very smooth transition from paper to PC.
Do you need interactivity?
Naturally, for interactive web animation, Flash is the way to go - although Silverlight may provide some competition in that area. If you don't need interactivity in your animations and intend to just let the user watch from beginning to end, then your options are a bit wider.
What is it missing?
Sometimes a program can have a dozen bonus features, but if it's missing something crucial it can be a deal-breaker. For instance, I can't use a 2D animation program that doesn't have onion-skinning; it's pretty useless to me. What's your number one must-have feature, and do the programs you've chosen offer it?
All right, I've narrowed it down to a few; what now?
Do a little more research. Read reviews from professionals and end-users; people tend to be a bit more honest about product advantages and failings than the marketing copy produced by the developers' PR department. Check to see if there's a free trial available, so you can try before you buy and see if you're comfortable working with the program. Think about anything else that might be important to you. Do you need technical support, and is that available for the programs you're looking at? Do you need the ability to integrate with a webcam?
These last few questions will let you pick the program that's right for you, and make sure you get the most value out of whatever you choose.
