This question is clearly very subjective. As other commenter's have said, a firm grasp of statistics requires years of academic study.
A few pointers:
First, even assuming that you don't want to go back to school, I always recommend looking at the statistics courses at the top 5 universities and following their syllabi for reading lists (here's one ranking of statistics departments). Particularly where universities have overlap in textbooks, that can be a good indication of a key text. Berkeley offers webcasts of many of their introductory courses (for instance, Stats 2 Introduction to Statistics), also available on iTunes.
If you were just going to get one book that covers computational statistics, I would suggest "Modern Applied Statistics with S" by Venables and Ripley (known as V&R). It is comprehensive and does a commendable job covering both the statistics and the programming (in the S langauge, which is used in both S-Plus and R). That said, it doesn't go into great detail on any subject (given that it covers everything in under 500 pages).
One of my favorite statistics textbooks (while not introductory) is "Data Analysis Using Regression and Multilevel/Hierarchical Models" by Andrew Gelman and Jennifer Hill. Their book also provides plenty of R examples, and fully meets your criteria for comprehension: Gelman is one of the best statistics teachers that I have encountered.
Peter Dalgaard's "Introductory Statistics with R" does a reasonable job of covering basic statistics and R in short order, but IMHO John Chambers' "Software for Data Analysis" is the best book on R itself.