We have been using salesforce.com for about 3 1/2 years now. What a great product. When it comes to CRM I would consider them the leader. A hosted solution, we have never had any trouble with availability or issues like that. It is a well designed product. BUT it is so #$#@ expensive. We pay $100 per month per user for the enterprise version and with 20-30 users you see how much that can add up too. That's still better than an in house solution that you need an admin to take care of. Cheaper than an admin for sure. But to add additional functionality like marketing automation or billing you have to add 3rd party products and that raises the price exponentially. Before long you price a small business right out of salesforce.com
Then I was introduced to infusionsoft.com. A great product with it's strength in marketing automation. But the CRM portion isn't even in the same league with salesforce.com. And it is $700 per month for 30 users, substantially less money and ecommerce and marketing automation included.
I came across this article comparing the two: http://www.thesaleswhisperer.com/salesforce-com-vs-infusionsoft-as-a-small-business-crm/