In International Space Station: Miguel Paraz voted up an answer.
The most significant difference, if we were to design the ISS today, is that we no longer have a Space Shuttle to assemble the vehicle. That would dramatically change the designs for all of the American, European, and Japanese modules for two major reasons: 1) We currently have no rockets that can carry modules as large as many of those on the ISS, so modules would become smaller and 2) Without the Space Shuttle to deliver the module directly to ISS, each module would have to be designed to have its own guidance, navigation, and control system (as the Russian modules do). That raises cost, complexity, and payload mass and introduces risk because of the presence of explosive materials and toxic chemicals.
There have been no major technological innovations that would dramatically change ISS. An important point to appreciate about spacecraft technology is that it only really evolves dramatically when usage requires it do so. The changes have been incremental. For example, in 2013, there is no better alternative to using solar power for the ISS than there was in 1993. Solar cell technology has incrementally improved, so the solar arrays we would design today would hopefully be a little more compact. The biggest cause of stress, for us, with the solar arrays, has been a concept called longeron shadowing. There is a delicate truss structure that holds the solar arrays together. It has to be delicate or it would be too massive – but its delicacy makes it susceptible to damage when the temperature across the truss varies sharply, because part of the truss is in the sun and part is shadowed by another solar array. Knowing what we know today, I think we would re-design that truss a little – we would probably coat it with a thermal resistant paint.
There is no need to change the propulsion mechanism. Today, there might be consideration of incorporating ion jet engines - but they aren't really yet mature enough to be used instead of the current systems.
Many of the other changes are also "if we knew then what we know now" changes - so if ISS had not existed, we probably wouldn't fix for a new design. I think we would probably try to design the US/ESA/JAXA modules to use something other than ammonia in the external thermal control system. The ammonia never actually enters the vehicle, but it rubs up against the water lines that do go inside the vehicle. Heat from the water is conducted into the ammonia. There is a tiny possibility that a crack could form and ammonia could infiltrate the water and get inside the vehicle. Should that ammonia then get into the air, the crew could die. Because of that, we spend a lot of time training the crew to deal with an emergency toxic atmosphere scenario. The lifetime training costs for that will likely outweigh the added design costs of not using ammonia. The Russians do not use ammonia. They use polymethyl siloxane (anti-freeze). Although not something you want to drink, it is considerably less toxic (Dominos Pizza uses it in their cheese).
There are probably several changes we would like to make related to redundancy, but the need for those changes would have only been identified by flying ISS. If we were building the first ISS, now, we wouldn't realize them. We would probably use a greater amount of smaller CMGs (Control Moment Gyroscopes).
Noise is a problem on ISS. There is no natural convection, in space, so we have to have forced convection to circulate the air. This means that there are many, many fans aboard the ISS. There are fans to move air from one module to another, there are fans to move air through racks, and there are fans to cool individual pieces of hardware. Imagine being in a sealed room with one hundred computer fans, all whirring as if the computers are being used to play games. Economically, I don't know if we really would change the design – but I would like to see us use silent fan technology like that used by the Dyson company.
One change that technological evolution would have probably led to, is that, today, we probably would use LED lighting instead of fluorescent bulb lighting. It would save power, be a lot safer, have less mass, and provide more options for adjustment by the crew. Research into circadian rhythms has led us to change the type of bulbs we use, but LEDS would allow variable adjustments.
The crew would like modifications made to how storage is handled aboard ISS so that less equipment is stored loose/bungeed to walls.
The original ISS assembly sequence included a dedicated habitation module, called TRANSHAB. TRANSHAB was to be an inflatable module. It could have served as an excellent testbed for later use of inflatable modules in a Mars mission. Unfortunately, there were a few members of Congress that objected to NASA spending any money on anything Mars related, so TRANSHAB ended up being killed by Congress. Bigelow later took the TRANSHAB design and has built his business from it and there are plans to attach one of Bigelow's inflatable modules to ISS. I would assume that a station designed today would use some inflatable modules. The entire station would not be inflatable, however, as they don't provide structural strength for a long stack, don't provide good meteor protection, and don't provide good radiation protection. Inflatable modules would likely project off of the spine.
Layout in general would not change considerably. If we are going to assemble a station over a period of time, and yet use it while it is being assembled, there aren't a lot of options. Building along a single axis provides stability of both structure and attitude control of that structure. Solar arrays need to have unobstructed view of the sun. The aerodynamic and gravitational cross-sections need to be fairly balanced to avoid unwanted torques. The approach corridors for visiting vehicles need to be unobstructed and for ease of orbital mechanics should be along either the r-bar (z-axis) or v-bar (x-axis).
As long as the Russians are a partner, the orbit would be required to be the current orbit (inclination of 51.6 degrees). It just isn't economically feasible to have them fly to lower inclinations.
The major changes if we were to shift the focus from lab to waystation would be to have ports that could support larger vehicles along with truss that would run alongside such a vehicle so that the robotic arm could move up and down the vehicle and help assemble it. We would also need capabilities to transfer consumables (like fuel, air, and water) to the vehicle that is visiting.See question on Quora