If your definition of "human" fits anywhere close to the current norms for human physical form - a leg-to-body ratio of approximately 4:3 for instance - and the shape isn't radically different then the laws of physics will be pretty stern limiting factors.
The current peak of human running speed is of course the records set by Usain Bolt in the 100m and 200m sprints, both of which he clocked in excess of 23.3+ mph. He and his teammates achieved a higer average speed in the 4x100m relay, since the runners in all but the initial 100m leg were already moving at handover, giving them ~24.3 mph overall. If we take out the inital 100m leg then I imagine we could get peak speed around 25 mph. In the last 100m of his Manchester 150m record in 2009 his average speed was around 25.7 mph. Fun fact: that's about 8 mph faster than a road runner, apparently.
Longer distance running is by necessity slower, since humans cannot sustain a sprint for long. The world record for the marathon is currently held by Eliud Kipchoge of Kenya who ran the Berlin Marathon in 2:01:39, for an average speed of 12.9 mph. He has recorded better times but under different circumstances. Go up to the ultras and the average speed drops again to only 10.1 mph over 100 miles.
These are the top achievements of unmodified human athletes as of right now. While I have no doubt that they will be beaten at some point I think it's unlikely that we'll see sustained speeds above 25 mph over 100 yards any time soon.
There are several factors that affect how fast a human can move and for how long.
Usain Bolt is 6'4" tall - same height as me funnily enough. He has a long stride capacity, although he shortened his stride to improve power delivery. A human who was a directly scaled down version of Bolt would have a shorter stride and therefore would move slower.
Sprinting mostly uses white muscle since it requires explosive speed rather than long-term endurance or raw power. Marathon runners tend to use both red and white muscle.
Energy and Oxygen
Energy for running comes from the available carbohydrates in the blood and those that can be released by the liver on short notice. Blood oxygen levels must maintained very high for sprinting.
This includes both cooling (waste heat) and purging metabolites from the muscle tissue while they are operating. Every time a muscle contracts it produces metabolites that have to be moved out of the cells to allow them to continue to function. Anaerobic metabolism produces byproducts like lactic acid and inorganic phosphate which contribute to fatigue and pain.
Now we're down to some really interesting bits. The spinal nerves that carry signals to your muscles do so at about 268 mph. Sounds pretty fast. The rest of the nervous system, the feedback and control impulses required just to keep your coordination and stop you from pitching sideways into a lamp post, can travel quite a bit slower. The nerves that carry proprioception (the REAL 6th sense) data work about the same speed.
This one is hard to put into numbers but it's still a limiting factor. Related to the nerve speed issue is the processing required in your brain - generally well below the level of consciousness - to control the entire process. While some parts of the process are simple feedback control systems there's a lot that needs to be handled. Data from the eyes feed into internal models of the next few steps to ensure you don't stumble on a slight rise or drop in the terrain. Wind pressure on the body joins visual and balance data to help you make adjustments in your stride placement and so on to avoid the afore-mentioned pitching sideways. And so on. If you can't process the data fast enough then you're in for a bad fall.
And that's not all. But it's enough to get started.
Essentially you need to address all of the above points in a way that doesn't turn your speedster into something so different that it can't be called human any more.
For the Flash there are two degrees of changes: the physical changes that improve his handling of all of the above points, plus a magical ability to alter the flow of time around himself. Even without leaning on the Speed Force (apparently all the good names were taken) Barry has improved reflexes and speed, enough so that he really shouldn't ever take a hit unless he can't see it coming. The 'downside' is that his metabolism is always running at a slightly higher time scale which is why he heals fasts, eats way too much and can't get drunk except on impossibly strong booze.
If you don't want to have to give your speedster the ability to warp time like a boss then you'll need something more like this:
- Lengthen the legs and alter the muscle attachments to more efficiently articulate them.
- Adjust the foot to be a better spring-loaded shock absorption system than it already is.
- Change the muscle to something far quicker and stronger. Somehow.
- Swap out the blood for something with a much better ability to carry both oxygen and fuel.
- Drastically improve the removal of waste products - again including heat - from the muscles.
- Replace the nerves with a more efficient direct electrical system.
- Improve the brain's processing ability significantly.
- Aerodynamics. Just saying.
Of the lot of them only re-articulating the legs will necessarily make a major difference in appearance. Humans come in all sorts of shapes and sizes so having bulging speedster muscles shouldn't be too much of a problem. Oh, and don't stint on the upper body either. Upgrade all of the muscles and nerves there too, since correct upper body motion can greatly increase the efficiency of running.
With all of the above, and assuming we're still working inside the physical laws here, it should be possible to get 3-4 times the top speed. A human-like construct running at up to 100 mph? That's Steve Austin level speed! No, not the wrestler.
As long as you don't want to break the rules too badly that's probably about it. Yeah you could get some minor gains by changing gait from sprinting to bounding, but you need to keep contact with the ground as much as possible or lose the ability to adjust.
At this point I'm pretty far out from "science-based" that I'n sure I'm going to get some down-votes for that alone, so I'll leave it there.