At first glance, the idea of having a Dominion handicap seems strange to me. I guess I just don't understand the psychology of it. If Bob is frustrated because he always loses at Dominion, is he really going to feel better about himself if he barely wins with a handicap? Because it seems like its 100% clear to anyone with half a brain (including Bob) that Bob played just as poorly as he would have without a handicap, and that the win is totally artificial. If Bob takes any extra satisfaction from "winning" with a handicap, it seems to me that Bob should be able to take the same satisfaction by playing without a handicap and striving to lose by fewer points. So I'm trying to think about what actually changes with any kind of Dominion handicap that makes it more appealing to anyone involved.
For example, consider a gold handicap. Two golfers might compete on the same course, but one starts off at a closer tee. This makes sense to me for the following reason. What do golfers pride themselves on? Well, barring Happy Gilmore, its probably not their brute strength. Most golfers probably take more pride in their accuracy, precision, putting/chipping, etc. So if you have two golfers with a huge strength difference, its probably not very interesting for either of them if one of them always wins due to brute strength factors. So having different tee locations allows them to still compete based on technique while correcting for strength differences.
So, back to Dominion, what skills are you trying to adjust for when you give a player a handicap. The best I can think of is that a player might be bad at analyzing the tableau, but somehow they are still competent with making in game decisions. For example, one problem with playing players of different skill is that if the inferior player makes poor choices early on, the end game just becomes super dull. If they're not even close to you in score, there's no interesting tension as to when to buy provinces vs switching to duchies. If there's no threat of them making a comeback, the timing for switching to VPs stops being interesting for both parties. If I'm winning the province battle 5-0 in a typical game, and my opponent decides its time to start buying duchies over gold, I feel like the rest of the game is pretty much a huge waste of time. So, in that sense, anything you can do to make the game closer results in a more satisfying end game for the entire table.
So I guess I've kind of just changed my mind about the potential value of Dominion handicaps mid post, which is fun, but there's still a bit of a caveat. Mainly that I'm a little skeptical that a player who is bad enough to need a handicap is going to have the late game awareness to make the endgame interesting even with a handicap. And if you have to adjust the handicap so much that they can be "competitive" without being able to analyze the tableau or make good late game decisions, then I think you're back to getting pretty much no value out of the handicap.
Personally, the most interesting and useful "handicap" from my point of view is arguably not a true handicap at all. If I was routinely playing with people who were frustrated from losing all the time, I think the best thing to do would be to stop before the game begins and jointly analyze the board. Point out what strategies you see as viable. Ask them what they see and talk about why it may or may not work. This will hopefully put them on the right track for a reasonably competitive game without any artificial junk, plus it will teach them a lot more than an otherwise handicapped game would. Along with this, go over a game afterwards and talk about what did and didn't work and why, along with how everyone might adapt their strategy in a subsequent play.
tl;dr I can see some value in a Dominion handicap, but it seems like a generally poor substitute for actually trying to teach the inferior player better strategy.