Absolutely, it makes a difference. I wrote a full-scale color RPG for the TI-84+CSE, and let me tell you, without optimizing any of my code, the game would flat out not run. At present, on the CSE, Sorcery of Uvutu can only run if every other program is archived and all other memory is out of RAM. The programs and data storage alone takes up 20k bytes in RAM, or just 1kb under all of available user memory. With all the variables in use, the memory approaches dangerously low points. I had points in my development where due to poor optimizations, I couldn't even start the game without getting a "memory all gone" error. I had plans to implement various extra things, but due to space and speed concerns, it was impossible to do so. That's only the consideration to space.
In the speed department, the game became, and still is, slow in the overworld. Walking around in the overworld is painfully slow compared to other games, and that's because of what I have to do in that code; I have to check for collisions, check if the user is moving to a new map, check if they pressed a key that should illicit a response, check if a battle should go on, and more. I was able to make slight optimizations to the walking speed, but even then, I could blatantly tell I had made improvements. It still was pretty awfully slow (at least compared to every other port I've made), but I made it a little more tolerable.
In summary, through my own experiences crafting a large project, I can say that in TI-Basic, optimizing code does make a difference. Other answers mentioned this, but TI-Basic is an interpreted language. This means the code isn't compiled into faster, lower level code, but the stuff that you put in the program is read straight out as it executes, is interpreted by the interpreter, calls the subroutines and other stuff it needs to to execute the commands, and then returns back to read the next line. As a result of that, and the fact that the TI-84+ series CPU, the Zilog Z80, was designed in 1976, you get a rather slow interpreter, especially for this day and age. As such, the fewer the commands you run, and the more you take advantage of system weirdness such as Ans being the fastest variable that can also hold the most types of data (integers/floats, strings, lists, matrices, etc), the better the performance you're gonna get.
Sources: My own experiences, documented here: https://codewalr.us/index.php?topic=778.msg27190#msg27190
TI-84+CSE RAM numbers came from here: https://education.ti.com/en/products/calculators/graphing-calculators/ti-84-plus-c-se?category=specifications
Information about the Z80 came from here: http://segaretro.org/Zilog_Z80