what changes when your input is giga/terabyte sized?
While some languages have naturally lower memory overhead in their types than others, that really doesn't matter for data this size - you're not holding your entire data set in memory regardless of the language you're using, so the "expense" of Python is irrelevant here.  As you pointed out, there simply isn't enough address space to even reference all this data, let alone hold onto it.
What this normally means is either a) storing your data in a database, or b) adding resources in the form of additional computers, thus adding to your available address space and memory.  Realistically you're going to end up doing both of these things.  One key thing to keep in mind when using a database is that a database isn't just a place to put your data while you're not using it - you can do WORK in the database, and you should try to do so.  The database technology you use has a large impact on the kind of work you can do, but an SQL database, for example, is well suited to do a lot of set math and do it efficiently (of course, this means that schema design becomes a very important part of your overall architecture).  Don't just suck data out and manipulate it only in memory - try to leverage the computational query capabilities of your database to do as much work as possible before you ever put the data in memory in your process.
I just took my first baby step today into real scientific computing today when I was shown a data set where the smallest file is 48000 fields by 1600 rows (haplotypes for several people, for chromosome 22). And this is considered tiny.
I write Python, so I've spent the last few hours reading about HDF5, and Numpy, and PyTable, but I still feel like I'm not really grokking what a terabyte-sized data set actually means for me as a programmer. 
For example, someone pointed out that with larger data sets, it becomes impossible to read the whole thing into memory, not because the machine has insufficient RAM, but because the architecture has insufficient address space! It blew my mind.
What other assumptions have I been relying in the classroom that just don't work with input this big? What kinds of things do I need to start doing or thinking about differently? (This doesn't have to be Python specific.)