Well, "On the origin of species" was published in 1859. If we assume that for humans a generation is approximately 20 years, that means that there have been between seven and eight generations since 1859. That is nowehere near enough time to observe evolutionary changes.
So, in answer to your question, not very different at all.
I think I need to clarify my answer. When we talk about a species evolving or a species being different today than it was X years ago, we are referring to the species as a whole. Of course evolution is an ongoing process, selective pressures are shaping our gene pool constantly. However, in order to say that humans are different today to those of 1859, we would need to show that the prevalence of particular genotypes has changed. That a specific trait (a gene or a mutation in a gene) has become "fixed", or, at the very least, that it has spread to a significant percentage of the population.
@niallhaslam's answer gives a link to a wired.com article about genetic resistance to HIV. This is not something that has recently evolved in response to HIV but is the result of an ancestral mutation. The article itself states that:
Using formulas that estimate how long genetic mutations have been
around, researchers have discovered that the mutation dates to the
Granted, this could be a good example of selection in action. If, after many, many more generations, this mutation has spread to the majority, or a significant percentage, of the population, we could point to it as an example of how humans have changed under the selective pressure of HIV infection. In order for this to happen, HIV will have to become common enough that having a resistance to is beneficial to a very large subset of humanity. I would expect to see such selective pressure in, for example, countries like South Africa where 12% of the population is HIV positive. Such pressure, however, will be negligible in countries with lower infection rates. In the US, for example, a recent study found HIV incidence among persons aged 13 years and older to be 42,200–54,000. Since the US has ~312 million people, 54,000 represents ~0.02% of the population. This will not provide enough of a selective pressure to observe differences in the short term evolutionary scale.
We do not, in fact, "evolve quickly in response to parasites viruses etc". Pathogens may apply selective pressure yes. But this is not a quick process. In any case, we do not evolve in response to them. Mutations occur, randomly usually, and if they confer an advantage they may be selected for. Said advantage may be because they confer resistance to disease but even then, the original mutation was not "in response" to the pathogen, However, such selection happens over many successive generations and will spread relatively slowly (quickly by evolutionary standards perhaps, but still slow for us, and certainly slower than 7 generations) across the population. The same holds true of epigenetic changes. Even if they can (as now seems likely) be transmitted down the generations, any selective advantage they confer will still act at the generational level.
So, while we are, of course, constantly evolving, there are no significant differences between the humans of today and those of Darwin's times. Sure, some genotypes may exist today that did not then and vice versa. These, however, are not representative of the species' genome. They may become so after many generations but, even if they exist, they have not had time to propagate through the gene pool and cannot be taken as evidence that H. sapiens as a species is "different" today.