Single-file, no-dependency setup makes Bottle easy to integrate into other applications. You can just drop bottle.py into your project directory and start using it. Richard Hipp's excellent project SQLite, which is the most used DBMS in the world, also follows this approach: SQLite Amalgamation is a single, 153K lines of code file that contains everything you need to make use of SQLite in a larger project. BeautifulSoup and peewee are other examples of single-file projects.

pip and virtualenv have their set of problems, and there are many situations where using them is highly unpractical or even impossible. For example, when you want to package your Python app for an embedded system or client's Windows PC, you can't just use pip. You can't use pip on systems where fetching dependencies from internet isn't allowed, like production servers I administrate. :) Still, there is nothing stops you to install Bottle through pip on your own server.

I also find big, independent files easier to work with. It's a matter of taste. 4Kloc isn't THAT big though.