Your questions are below in bold and are potentially rephrased slightly
I guess I’m asking for insider knowledge here … hopefully someone feels generous … I’m having difficulty turning my PI setup into any kind of sizable, on-going profit. I’ve considered a couple reasons why that might be, which leads me to seek out wisdom regarding:
1- is the difference between setting up on high-sec planets and low-sec planets enough to explain why my high-sec PI seems so lackluster?
Define lackluster. What kind of returns are you getting? In High-sec the best opportunities are likely T1 extractions and you might consider a T2 factory planet but I would be focused on maximizing one product to develop hone your skills. See how things work. Be absolutely sure to maximize your Command Center skills. This is crucial. To my mind, I would predict that in high sec for a T2 factory planet you could do Construction Blocks using products from a Gas and Barren planet, Coolant (Multiple sources), Nanites (Multiple sources), or Test Cultures (Multiple Sources). All of the above, provide you will multiple options with products that will sell at decent prices.
In high sec, I would avoid trying to get too complicated. Again, just try to maximize your outputs. Learn how it all works. Practice. Then move to low or if you are with a corporation null or wormhole space.
However, make sure your tax rate is 10% or less. That is a big problem in high sec. Null sec conglomerates put up POCOs in high sec and charge sometimes 25%, I think primarily as a market control. Additionally the resource itself in high sec is of lower quality (concentration) than in low sec.
As a rule the quality of PI goes higher from high to low to null to WH, I believe but don’t quote me on the last two.
What are the risks for low-sec PI? Is it possible for someone to come and either steal or destroy your infrastructure?
No one can steal or destroy your planetary infrastructure. You can lose materials stored in POCOs if they are destroyed and you might lose them if they change hands i.e. are sold to another corporation. I’m not sure about the latter so confirm this with someone else. The primary risk is ship loss while collecting and moving materials but this can be mitigated by:(1) avoiding patterns to your collections; (2) minimizing times at POCOs; (3) setting up SAFE points in your low sec systems and warping to those first cloaking up and doing your POCO launches from the SAFE points while cloaked!. Note: DO ALL OF your transfers to and from planets to POCOs at your safe points. You’ll have to warp to the POCOs to drop things off and pick them up, obviously but you should be able to no more than about 10 seconds there before you warp back to either a safe point or another POCO. Warp to the POCO, quickly make your pickup and warp away as soon as you can. I have found that a fast aligning (6 second Epithal) is the best ship for collecting PI materials. This is my opinion. Others may have better fits, better ideas. ASK them. Personally I would not rely on tank because you will die. Expensive ships used for PI collection is to me not a good idea. In low sec however you will lose ships eventually. It is the price of doing business but it will pay off.
2- am i just building the wrong PI product?
Certain products tend to sell more quickly than others. Make sure you look at the Show info tab for each product and look in View industry to see what they are used for. That will tell you basically how many products and which ones they are used for. The T2 products I listed above are used fairly extensively - construction blocks for T2 ship construction, nanites for nanite paste, coolant for fuel blocks, and test cultures for capital and Navy issue ship construction.
Anyone care to share insights on what makes the most money right now?
What makes the most money now will be different from what makes money tomorrow. Keep your goods until the market goes up and sell them when the market goes up. Don’t worry so much about the market today unless you need to for some reason. If you need the ISK, sell at what the market will bear. If not, wait or put in a market order for 3 months and see if your materials will sell at the price you set. Look at the sell and buy prices and the volumes sold and the trends in the market and try to figure out how the price might change over time. That can help you predict your sell price. Be patient. Or don’t if you need capital! Remember. Sometimes you’ll need the ISK for new equipment or maybe ammo to blow something up YEAHHH!!! 8)
3- does anyone have experience with building out an even broader setup using alts? is that necessary in order to see a worthwhile return?
I have some limited experienced. My planetary operations are in low sec. I have lost three ships doing PI - many others while doing other things but 3 specifically doing PI. What do you see as a worthwhile return? I plan on revising my PI productions and believe I can make a lot more than I do. I probably make at least 50 to 100 million every week to 10 days per character. That’s a conservative estimate of what I make. I am sure I can make much more if I organize things properly. That is a reasonably honest assessment of what I do with PI. Am I experienced? If my advice seems sound take it. If it works, then I would say I probably am experienced or just give good advice. 8) Let me know in game if you get the chance.